The Effect of Cox-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer
Final rept. 1 Jun 2001-31 May 2004
OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
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Aromatase CYP-l9 is responsible for estrogen biosynthesis within breast tumor tissue. Aromatase and cyclooxygenase-2 COX-2 are both overexpressed in human breast cancer, and increased levels of prostaglandin PG activates the CYP19 promotor and increases gene expression. We hypothesize that celecoxib, a selective COX-2 inhibitor, will decrease PG, decrease the expression of CYPl9, and reduce estrogen biosynthesis within tumor tissue. To test this hypothesis, in DOD grant DAMD17-C-01-0589, tumor tissue will be collected from breast cancer patients at the initial diagnosis, and again at the definitive surgery lumpectomy or mastectomy for breast cancer. In the 10-14 day interval before the definitive surgery, patients will receive celecoxib and tissue samples collected before and after treatment with celecoxib will be evaluated for gene expression of COX-2 and CYPl9. If our hypothesis is correct, then expression of the CYPl9 gene will decrease in response to celecoxib. This study will provide preliminary data to a support a mechanism whereby COX-2 inhibitors decrease estrogen production within breast tumors by decreasing CYP19 expression and b provide the rationale for initiating larger chemoprevention and therapeutic trials of COX-2 inhibitors in high risk and breast cancer patients.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research