Accession Number:

ADA426818

Title:

The Effect of Cox-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer

Descriptive Note:

Final rept. 1 Jun 2001-31 May 2004

Corporate Author:

OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS

Report Date:

2004-06-01

Pagination or Media Count:

9.0

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.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE