INVESTIGADORES
COCCA Claudia Marcela
artículos
Título:
Enhancement of BRCA1 gene expression by the peroxisome proliferator-activated receptor gamma in the MCF-7 breast cancer cell line.
Autor/es:
MIGUEL PIGNATELLI; CLAUDIA COCCA; ANGEL SANTOS; ANA PEREZ-CASTILLO
Revista:
ONCOGENE
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Año: 2003 vol. 22 p. 5446 - 5450
ISSN:
0950-9232
Resumen:
BRCA1 has been linked to the genetic susceptibility of a majority of
familial breast and ovarian cancers. Several lines of evidence indicate
that BRCA1 is a tumor suppressor and its expression is downregulated in
sporadic breast and ovarian cancer cases. Therefore, the identification
of genes involved in the regulation of BRCA1 gene expression might lead
to new insights into the pathogenesis and treatment of these tumors.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a
member of the nuclear receptor superfamily that has well-established
roles in the regulation of adipocyte development and glucose
homeostasis. More recently, it has been shown that ligands of PPARgamma
have a potent antitumorigenic activity in breast cancer cells. In the
present study we have found that two distinct ligands of PPARgamma;
15-deoxy-delta-(12,14)-prostaglandin J2 (15dPG-J2) and rosiglitazone,
increase the levels of BRCA1 protein in human MCF-7 breast cancer
cells. Immunofluorescence microscopy analysis showed that, after
treatment with 15dPG-J2, the BRCA1 protein is mainly localized in the
nucleus. Functional analysis by transient transfection of different
5'-flanking region fragments, as well as gel mobility shift assays and
mutagenic analysis, suggests that the effects of 15dPG-J2 and
rosiglitazone are mediated through a functional DR1 located between the
nucleotides -241 and -229, which is a canonical PPARgamma type response
element. Our data suggest that PPARgamma is a crucial gene regulating
BRCA1 gene expression and might therefore be important for the BRCA1
regulatory pathway involved in the pathogenesis of sporadic breast and
ovarian cancer.