INVESTIGADORES
PROIETTI ANASTASI Cecilia Jazmin
artículos
Título:
Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation
Autor/es:
SALATINO M, BEGUELIN W, PETERS MG, CARNEVALE R, PROIETTI CJ, GALIGNIANA MD, VEDOY CG, SCHILLACI R, CHARREAU EH, SOGAYAR MC, ELIZALDE PV
Revista:
ONCOGENE
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Año: 2006
ISSN:
0950-9232
Resumen:
Progestin regulation of gene expression was assessed in the progestin-dependent murine tumor line C4HD which  requires MPA, a synthetic progestin, for in vivo growth and expresses high levels of progesterone receptor (PR). By using suppressive subtractive hybridization, caveolin-1 was identifed as a gene whose expression was increased with in vivo MPA treatment. By Northern and Western blot analysis, we further confirmed that caveolin-1 mRNA and protein expression increased in MPA-treated tumors as compared with untreated tumors. When primary cultures of C4H D cells were treated in vitro with MPA, caveolin-1 levels also increased, effect that was abolished by pre-treatment with progestin antagonist RU486. In addition, MPA promoted strong caveolin-1 promoter transcriptional activation both in mouse and human breast cancer cells. We also showed that MPA regulation of caveolin-1 expression involved in activation of two signaling pathways: MAPK and PI-3K. Short-term MPA treatment of C4HD cells led to tyrosine phosphorylation of caveolin-1 protein, where Src was the kinase involved. Additionally, we showed that MPA-induced association ofcaveolin-1 and PR, which was detected by coimmunoprecipitation and by confocal microscopy. Finally, we proved that MPA-induced proliferation of C4HD cells was inhibited by suppression of caveolin-1 expression with antisense oligodeoxynucleotides to caveolin-1 mRNA. Furthermore, we observed that inhibition of caveolin-1 expression abrogated PR capacity to induced luciferase activity from a progesterone response element driven reporter plasmid. Comprehensively, our results demonstrated for the .rst time that caveolin-1 expression is upregulated by progestin in breast cancer. We also demonstrated that caveolin-1 is a downstream effector of MPA that is partially responsible for the stimulation of growth of breast cancer cells.