Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells.
We have analyzed the expression of the breast cancer susceptibility gene, Brca2, in mammary epithelial cells as a function of proliferation and differentiation. Our results demonstrate that Brca2 mRNA expression is tightly regulated during mammary epithelial proliferation and differentiation, and that this regulation occurs coordinately with Brca1. Specifically, Brca2 mRNA expression is up-regulated in rapidly proliferating cells; is down-regulated in response to serum deprivation; is expressed in a cell cycle-dependent manner, peaking at the G1/S boundary; and is up-regulated in differentiating mammary epithelial cells in response to glucocorticoids. In each case, an identical pattern of expression was observed for Brca1. These results indicate that proliferative stimuli modulate the mRNA expression of these two breast cancer susceptibility genes. In addition, the coordinate regulation of Brca1 and Brca2 revealed by these experiments suggests that these genes are induced by, and may function in, overlapping regulatory pathways involved in the control of cell proliferation and differentiation.
Rajan
J V
JV
Department of Molecular and Cellular Engineering, Stellar-Chance Laboratories, University of Pennsylvania School of Medicine, Philadelphia 19104-6069, USA.
Wang
M
M
Marquis
S T
ST
Chodosh
L A
LA
D000818:Animals; D019313:BRCA1 Protein / Q000096:biosynthesis*; D024682:BRCA2 Protein; D001940:Breast / Q000166:cytology* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011388:Prolactin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D005819:Genetic Markers; D007328:Insulin; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D011388:Prolactin; D006854:Hydrocortisone