Cell cycle control of BRCA2.
Identifying the conditions and kinetics of the induction of BRCA2 gene expression may implicate roles for the function of the tumor suppressor gene. In this study, expression of BRCA2 mRNA is shown to be regulated by the cell cycle and associated with proliferation in normal and tumor-derived breast epithelial cells. Cells arrested in G(0) or early G1 contained low levels of BRCA2 mRNA. After release into a proliferating state, cells produced maximum levels of BRCA2 mRNA in late G1 and the S-phase. Similar cell cycle control of BRCA2 was observed in fractions of exponentially growing cells isolated by centrifugal elutriation. Expression of BRCA2 was shown to be independent of bulk DNA synthesis. In addition, the kinetics of BRCA2 mRNA up-regulation appeared to be similar to those of BRCA1, suggesting that the two genes could be commonly controlled. These results imply that these two tumor suppressor genes are utilized during growth and may have a protective role in cellular proliferation.
Vaughn
J P
JP
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cirisano
F D
FD
Huper
G
G
Berchuck
A
A
Futreal
P A
PA
Marks
J R
JR
Iglehart
J D
JD
D000328:Adult; D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004791:Enzyme Inhibitors; D006657:Histones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D008148:Lovastatin