Brca1 regulates in vitro differentiation of mammary epithelial cells.
Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.
Kubista
Marion
M
Prenatal Diagnosis and Therapy, Obstetrics and Gynecology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Rosner
Margit
M
Kubista
Ernst
E
Bernaschek
Gerhard
G
Hengstschläger
Markus
M
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D012333:RNA, Messenger