Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G2/M checkpoint signaling
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Christoforos G. Thomas Anders Strom Karolina Lindberg Jan-Ake Gustafsson
- چاپ و سال / کشور: 2010
Description
Estrogen receptor beta (ERb) inhibits proliferation in different cellular systems by regulating components of the cell cycle machinery. Eukaryotic cells respond toDNA damage by arresting inG1, S, orG2 phases of the cell cycle to initiate DNA repair. Most tumor cells due to disruptions in the p53-dependentG1 pathway are dependent on S-phase and G2/M checkpoints to maintain genomic integrity in response toDNAdamage.We report that induction of ERb expression causes abrogation of the S-phase, and the Chk1/Cdc25Cmediated G2/M checkpoints after cisplatin and doxorubicin exposure in p53-defective breast cancer cells but not in p53 wild-type mammary cells. This impairment of DNA damage response that involves BRCA1 downregulation and caspase- 2 activation results in mitotic catastrophe and decreased cancer cell survival. These results indicate that in cancers where p53 is defective, assessment of the presence of ERb may be of predictive value for the successful response to chemotherapy.
Breast Cancer Res Treat (2011) 127:417–427 DOI 10.1007/s10549-010-1011-z Received: 19 June 2010 / Accepted: 22 June 2010 / Published online: 10 July 2010 Springer Science+Business Media, LLC. 2010
