Role of Cdc37 in Breast Cancer
Final rept. 1 Jul 1997-30 Jun 2000
TUFTS UNIV BOSTON MA
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Here we have studied a novel growth related protein called Cdc37. We have found that Cdc37 hinds to Raf-1 and the Cyclin D partner protein Cdk4. We have examined the role of Cdc37 in Raf-1 signaling and in estrogen receptor function. We have found that Cdc37 is required for the function of Raf-1 in mammalian cells. In addition, we have found that inhibition of Cdc37 also inhibited estrogen function in the human MCF-7 breast cancer cell line. Moreover, we have investigated the potential role of Cdc37 in breast cancer. Cdc37 protein expression was found in all breast cancer cell lines examined. We have also found that the drug geldanamycin which is an inhibitor of the Cdc37 partner protein HSP90 is a potent growth suppressor of the MCF-7 estrogen dependent breast cancer cell line. In a screen of human breast cancer cell lines, we have identified one cell line that has 3-4 copies of the CDC37 gene and has a high level of expression of the Cdc37 protein. These results suggest that drugs that would inhibit Cdc37 function may be effective in inhibiting breast cancer growth and would be expected to have fewer side effects than geldanamycin.
- Medicine and Medical Research