Cyclin C Regulation of the Stress Response and Drug Sensitivity in Breast Cancer
Final rept. 1 Aug 1997-31 Jul 2000
FOX CHASE CANCER CENTER PHILADELPHIA PA
Pagination or Media Count:
One mechanism by which malignancies are protected from cytotoxic agents is through aberrant activation of the stress response pathway. The yeast C-type cyclin UME3 is a repressor of stress response genes. To relieve this repression, the UME3 protein Ume3p is rapidly destroyed when cells are exposed to several types of stress. To determine if this novel regulatory strategy is conserved, the human C-type cyclin HcycC levels were monitored in cell lines exposed to stress and apoptotic inducers. An epitope tagged derivative of HcycC HcycC-HA was constructed and stability integrated into the human breast cancer cell line MCF-7. Exponential cultures were subjected to either heat shock 42C or exposed to tumor necrosis factor alpha TNFalpha. In both studies, HcycC levels were reduced compared to untreated controls. In addition, HcycC was rapidly destroyed when ectopically expressed in yeast subjected to heat shock. These findings are consistent with a model that down regulation of HcycC is part of the normal cellular response to stress. Moreover, these findings suggest that the regulation of C-type cyclins is conserved from yeast to man.
- Medicine and Medical Research
- Stress Physiology