A BRCA1 Mutant Alters G2-M Cell Cycle Control in Human Mammary Epithelial Cells

作者: Mei T. Lai , John L. Tonkinson , Jeffrey S. Larson

DOI:

关键词:

摘要: Mutations in BRCA1 increase the risk of breast and ovarian cancer. Although mechanism by which mutant alters growth regulation is unknown, COOH terminus appears to play a critical role. To examine this, we introduced vector expressing COOH-terminal residues 1293–1863 (CT-BRCA1) into nontumorigenic human epithelial cells. Overexpression CT-BRCA1 led reduction doubling time (from 64 44 h) decreased reliance on factors, suggesting that this may function dominant-negative manner. Expression induced alterations cell cycle control, mainly G2-M, including loss G2-M block colchicine. These results suggest one BRCA1-related control occurs governing checkpoint(s) between DNA replication mitosis.

参考文章(6)
Mark S. Chapman, Inder M. Verma, Transcriptional Activation by Brca1 Nature. ,vol. 382, pp. 678- 679 ,(1996) , 10.1038/382678A0
Marilyn E. Thompson, Roy A. Jensen, Patrice S. Obermiller, David L. Page, Jeffrey T. Holt, Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression Nature Genetics. ,vol. 9, pp. 444- 450 ,(1995) , 10.1038/NG0495-444
D Ford, DF Easton, The genetics of breast and ovarian cancer British Journal of Cancer. ,vol. 72, pp. 805- 812 ,(1995) , 10.1038/BJC.1995.417
John L. Tonkinson, Philip Marder, Sherri L. Andis, Richard M. Schultz, Lynn S. Gossett, Chuan Shih, L. G. Mendelsohn, Cell cycle effects of antifolate antimetabolites: implications for cytotoxicity and cytostasis Cancer Chemotherapy and Pharmacology. ,vol. 39, pp. 521- 531 ,(1997) , 10.1007/S002800050608
A. Berchuck, R. C. Bast, I. J. Jacobs, R. W. Wiseman, V. Leech, T. Harrington, A. Molyneux, B. A J Ponder, S. A. Smith, P. A. Futreal, R. J. Osborne, A Deletion Unit on Chromosome 17q in Epithelial Ovarian Tumors Distal to the Familial Breast/Ovarian Cancer Locus Cancer Research. ,vol. 53, pp. 1218- 1221 ,(1993)
Devilee P, Cornelis Rs, Cornelisse Cj, Kersenmaeker A, Khan Pm, Kuipers-Dijkshoorn N, van Vliet M, Bardoel A, Allele loss patterns on chromosome 17q in 109 breast carcinomas indicate at least two distinct target regions. Oncogene. ,vol. 8, pp. 781- 785 ,(1993)