BRCA1 expression is induced before DNA synthesis in both normal and tumor-derived breast cells.
Insight into the function of the BRCA1 tumor suppressor gene may be gained by studying its regulation. In this study, the expression of BRCA1 was examined as a function of the cell cycle in normal and tumor-derived breast epithelial cells. Cells arrested in G(zero) or early in G1 contained low levels of BRCA1 mRNA. After release, populations of cells reached maximal levels of BRCA1 in late G1 and S phase. Induction of BRCA1 was shown to occur before the onset of DNA synthesis by synchronizing cells at the G1-S boundary. Levels of the BRCA1 protein were regulated in a similar manner. No difference was observed between primary cultures of normal mammary epithelial cells and immortalized tumor-derived cell lines. These results suggest that BRCA1 may function at the G1-S checkpoint.
Vaughn
J P
JP
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Davis
P L
PL
Jarboe
M D
MD
Huper
G
G
Evans
A C
AC
Wiseman
R W
RW
Berchuck
A
A
Iglehart
J D
JD
Futreal
P A
PA
Marks
J R
JR
D000328:Adult; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D016193:G1 Phase / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D019398:Genes, BRCA1; D006801:Humans; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D017354:Point Mutation; D012016:Reference Values; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004247:DNA