The Effect of Cox-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA426818
Entities
People
- Charles L. Shapiro
- Robert Brueggemeier
- William Burak
Organizations
- Ohio State University