INVESTIGADORES
LAMB Caroline Ana
congresos y reuniones científicas
Título:
Interaction between Fibroblast Growth Factor Receptor (FGFR) and Progesterone Receptor (PR) in experimental breast cancer.
Autor/es:
CERLIANI, JUAN PABLO; LAMB, CAROLINE A.; LANARI, CLAUDIA
Lugar:
Denver, EEUU
Reunión:
Congreso; American Association for Cancer Research; 2009
Institución organizadora:
AACR
Resumen:
We have developed a murine model of breast cancer progression in which
ductal, hormone-dependent (HD) carcinomas transit through different stages of
hormone responsiveness retaining the expression of high levels of estrogen (ER) and
progesterone receptors (PR). Unlike HD carcinomas, hormone-independent (HI) tumors
do not need the exogenous administration of medroxyprogesterone acetate (MPA) to
grow. In vitro, however, there are no differences in hormone responsiveness between
both types, suggesting the involvement of host factors regulating in vivo tumor growth.
We have previously observed a) an increase in FGFR (1-4) expression, mainly
FGFR-2 and -3, in HI tumors and in HD tumors growing with MPA as compared with
untreated HD tumors; b) higher levels of FGF-2 in stroma from HI tumors; c) that the
pharmacological or genetic blockage of FGFR-2 with antiprogestins or SiRNA
respectively, inhibited the stimulation induced by carcinoma associated fibroblasts on
epithelial cell growth. We hypothesize that the stroma from HI tumors participates
regulating HI tumor growth by releasing FGF-2 that acts as a paracrine growth factor
which activates FGFR-2 in the epithelial cells, which in turn activates PR.
The aim of this study was to evaluate a direct interaction between PR and
FGFRs using our murine tumor model and human T47D cells. Purified epithelial cells
of C4-HI or T47D cells were seeded in chamber slides and after few days of culture,
they were starved in 1% charcoalized fetal calf serum and treated with FGF-2 (50
ng/ml), MPA (10-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
We have previously observed a) an increase in FGFR (1-4) expression, mainly
FGFR-2 and -3, in HI tumors and in HD tumors growing with MPA as compared with
untreated HD tumors; b) higher levels of FGF-2 in stroma from HI tumors; c) that the
pharmacological or genetic blockage of FGFR-2 with antiprogestins or SiRNA
respectively, inhibited the stimulation induced by carcinoma associated fibroblasts on
epithelial cell growth. We hypothesize that the stroma from HI tumors participates
regulating HI tumor growth by releasing FGF-2 that acts as a paracrine growth factor
which activates FGFR-2 in the epithelial cells, which in turn activates PR.
The aim of this study was to evaluate a direct interaction between PR and
FGFRs using our murine tumor model and human T47D cells. Purified epithelial cells
of C4-HI or T47D cells were seeded in chamber slides and after few days of culture,
they were starved in 1% charcoalized fetal calf serum and treated with FGF-2 (50
ng/ml), MPA (10-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
both types, suggesting the involvement of host factors regulating in vivo tumor growth.
We have previously observed a) an increase in FGFR (1-4) expression, mainly
FGFR-2 and -3, in HI tumors and in HD tumors growing with MPA as compared with
untreated HD tumors; b) higher levels of FGF-2 in stroma from HI tumors; c) that the
pharmacological or genetic blockage of FGFR-2 with antiprogestins or SiRNA
respectively, inhibited the stimulation induced by carcinoma associated fibroblasts on
epithelial cell growth. We hypothesize that the stroma from HI tumors participates
regulating HI tumor growth by releasing FGF-2 that acts as a paracrine growth factor
which activates FGFR-2 in the epithelial cells, which in turn activates PR.
The aim of this study was to evaluate a direct interaction between PR and
FGFRs using our murine tumor model and human T47D cells. Purified epithelial cells
of C4-HI or T47D cells were seeded in chamber slides and after few days of culture,
they were starved in 1% charcoalized fetal calf serum and treated with FGF-2 (50
ng/ml), MPA (10-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
We have previously observed a) an increase in FGFR (1-4) expression, mainly
FGFR-2 and -3, in HI tumors and in HD tumors growing with MPA as compared with
untreated HD tumors; b) higher levels of FGF-2 in stroma from HI tumors; c) that the
pharmacological or genetic blockage of FGFR-2 with antiprogestins or SiRNA
respectively, inhibited the stimulation induced by carcinoma associated fibroblasts on
epithelial cell growth. We hypothesize that the stroma from HI tumors participates
regulating HI tumor growth by releasing FGF-2 that acts as a paracrine growth factor
which activates FGFR-2 in the epithelial cells, which in turn activates PR.
The aim of this study was to evaluate a direct interaction between PR and
FGFRs using our murine tumor model and human T47D cells. Purified epithelial cells
of C4-HI or T47D cells were seeded in chamber slides and after few days of culture,
they were starved in 1% charcoalized fetal calf serum and treated with FGF-2 (50
ng/ml), MPA (10-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
In vitro, however, there are no differences in hormone responsiveness between
both types, suggesting the involvement of host factors regulating in vivo tumor growth.
We have previously observed a) an increase in FGFR (1-4) expression, mainly
FGFR-2 and -3, in HI tumors and in HD tumors growing with MPA as compared with
untreated HD tumors; b) higher levels of FGF-2 in stroma from HI tumors; c) that the
pharmacological or genetic blockage of FGFR-2 with antiprogestins or SiRNA
respectively, inhibited the stimulation induced by carcinoma associated fibroblasts on
epithelial cell growth. We hypothesize that the stroma from HI tumors participates
regulating HI tumor growth by releasing FGF-2 that acts as a paracrine growth factor
which activates FGFR-2 in the epithelial cells, which in turn activates PR.
The aim of this study was to evaluate a direct interaction between PR and
FGFRs using our murine tumor model and human T47D cells. Purified epithelial cells
of C4-HI or T47D cells were seeded in chamber slides and after few days of culture,
they were starved in 1% charcoalized fetal calf serum and treated with FGF-2 (50
ng/ml), MPA (10-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
We have previously observed a) an increase in FGFR (1-4) expression, mainly
FGFR-2 and -3, in HI tumors and in HD tumors growing with MPA as compared with
untreated HD tumors; b) higher levels of FGF-2 in stroma from HI tumors; c) that the
pharmacological or genetic blockage of FGFR-2 with antiprogestins or SiRNA
respectively, inhibited the stimulation induced by carcinoma associated fibroblasts on
epithelial cell growth. We hypothesize that the stroma from HI tumors participates
regulating HI tumor growth by releasing FGF-2 that acts as a paracrine growth factor
which activates FGFR-2 in the epithelial cells, which in turn activates PR.
The aim of this study was to evaluate a direct interaction between PR and
FGFRs using our murine tumor model and human T47D cells. Purified epithelial cells
of C4-HI or T47D cells were seeded in chamber slides and after few days of culture,
they were starved in 1% charcoalized fetal calf serum and treated with FGF-2 (50
ng/ml), MPA (10-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
in vivo tumor growth.
We have previously observed a) an increase in FGFR (1-4) expression, mainly
FGFR-2 and -3, in HI tumors and in HD tumors growing with MPA as compared with
untreated HD tumors; b) higher levels of FGF-2 in stroma from HI tumors; c) that the
pharmacological or genetic blockage of FGFR-2 with antiprogestins or SiRNA
respectively, inhibited the stimulation induced by carcinoma associated fibroblasts on
epithelial cell growth. We hypothesize that the stroma from HI tumors participates
regulating HI tumor growth by releasing FGF-2 that acts as a paracrine growth factor
which activates FGFR-2 in the epithelial cells, which in turn activates PR.
The aim of this study was to evaluate a direct interaction between PR and
FGFRs using our murine tumor model and human T47D cells. Purified epithelial cells
of C4-HI or T47D cells were seeded in chamber slides and after few days of culture,
they were starved in 1% charcoalized fetal calf serum and treated with FGF-2 (50
ng/ml), MPA (10-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
-8M) or vehicle for different periods of time. Confocal imaging showed
an intimate interaction between FGFR-2 and PR when the cells (C4-HI or T47D) were
treated with FGF-2 or MPA. Under these experimental conditions there was almost no
interaction between PR and FGFR-1, FGFR-3 or FGFR-4 (p<0.05). We showed that the
peak of co-localization was observed after 20 min of incubation (p<0.05) with MPA and
1 hour with FGF-2 in C4-HI cells or 20 min. with both treatments in T47D (p<0.05).
Inmunoprecipitation assays using C4-HI and T47D cells confirmed confocal
observations. In time course experiments (5, 10, 30 min., and 1 hour incubation with
FGF-2 50 ng/ml or MPA 10-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.
-8M) we have also observed that the increased pSer190
phosphorylation of PR in both cell types correlated with an activation of Erk and Akt
pathways, an increase in c-Myc expression and early phosphorylation of Stat-5 in both
models.
These results show for the first time nuclear interactions between FGFR-2 and
PR in two different breast cancer models suggesting that Stat 5 may be implicated in
this interaction. In addition, these data are in agreement with our hypothesis regarding
FGF-2 activating FGFR-2 in epithelial cells as a mechanism of PR ligand independent
activation indicating that FGFR, are potential targets in the treatment of hormone
related breast cancer.