Cyclin C Regulation of the Stress Response and Drug Sensitivity in Breast Cancer
Abstract
Disseminated malignancies are commonly treated with cytotoxic agents (e.g., chemotherapy, radiation) which target the unregulated growth associated with tumors. However, many of these procedures have proven unsuccessful due in part to the acquired resistance of cancer cells to these regimens. Mounting evidence suggests that one underlying mechanism by which malignancies are protected from cytotoxic agents is through aberrant activation of a pathway generally referred to as the "stress response". Using a genetic approach in yeast, we have identified a new C-type cyclin (UME3) that, when deleted, allows the inappropriate expression of the HSP70 family member SSA1. Several pieces of data suggest that the human cyclin C (cycC), which exhibits nearly 40% identity to the yeast gene, may also be involved in regulating the stress response. First, cycC co-localizes with the human RNA polymerase suggesting a role for this cyclin in transcriptional regulation. Second, when expressed in yeast, cycC is rapidly destroyed in cultures exposed to elevated temperatures. Finally, we have mapped cycC to a region of the genome (6q21) that is frequently deleted in breast tumors. This proposal will explore the relationship between cycC activity, the stress response and drug sensitivity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA368477
Entities
People
- Randy Strich
Organizations
- Fox Chase Cancer Center