Progesterone induces BRCA1 mRNA decrease, cell cycle alterations and apoptosis in the MCF7 breast cancer cell line.
BACKGROUND
Inherited mutations of the BRCA1 gene are responsible for hereditary breast and ovarian cancer syndrome. However, little is known of how disruption of BRCA1 functions preferentially increases cancer risk in hormone-dependent organs. We aimed to study whether BRCA1 was regulated by progesterone in the MCF7 breast cancer cell line.


METHODS
MCF7 breast cancer cells were incubated with 10(-4) or 10(-10) M progesterone for 24 or 48 hours. BRCA1 expression, proliferation and apoptosis were analysed.


RESULTS
10(-4) M progesterone decreased cell proliferation, cell cycle progression and induced apoptosis. In addition, BRCA1 and cyclin A mRNA decreased. In contrast, none of these effects were observed in MCF7 cells incubated with 10(-10) M progesterone.


CONCLUSIONS
The down-regulation of BRCA1 in MCF7 cells incubated with 10(-4) M progesterone seems to be a consequence of cell cycle alterations rather than a direct effect of the hormone on BRCA1.
Ansquer
Yan
Y
INSERM U 481, Faculté de Médecine Xavier Bichat, 75018 Paris, France. yan.ansquer@lmr.ap-hop-paris.fr
Legrand
Agnès
A
Bringuier
Annie-France
AF
Vadrot
Nathalie
N
Lardeux
Bernard
B
Mandelbrot
Laurent
L
Feldmann
Gérard
G
D017209:Apoptosis / Q000187:drug effects; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis
D019313:BRCA1 Protein; D016213:Cyclins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone