The Role of hCDC4 as a Tumor Suppressor Gene in Genomic Instability Underlying Prostate Cancer
Annual summary rept. 1 Nov 2004-31 Oct 2005
SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA
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This study investigates the role of a newly identified gene called hCDC4 in prostate cancer. The hCDC4 gene encodes a protein that functions in a cellular process called proteolysis, or protein degradation. hCdc4 degrades a protein called cyclin E1, which is a central component of the cell division machinery. Cyclin E1 is involved in initiating DNA replication in cells. However, in many types of human tumors cyclin E1 protein levels are aberrant and this phenotype has been shown in vitro and in vivo to be oncogenic. Very little is known regarding cyclin EhCdc4 in prostate tumors. We are exploring whether hCDC4 functions as a tumor suppressor gene in prostate cancer. We have completed a genetic screen of prostate tumors and found an hCDC4 gene mutation. We have shown that this mutant hCdc4 cannot bind cyclin el substrate in vivo. We are currently determining whether hCDC4 functions as a haplo-insufficient tumor suppressor through LOH and expression analysis.
- Anatomy and Physiology
- Medicine and Medical Research