MEHARRY RCMI PROGRAM IN WOMEN'S HEALTH RESEARCH

$2,206,999G12FY2006RRNIH

Meharry Medical College, Nashville TN

Investigators

Linked publications & trials

Paper 37182601 Paper 31359841 Paper 30353775 Paper 29679472 Paper 29173933 Paper 29131708 Paper 29076125 Paper 29049918 Paper 28834316 Paper 28780737 Paper 28595479 Paper 27967206 Paper 27602597 Paper 27389918 Paper 26951798 Paper 26820714 Paper 26765097 Paper 26358852 Paper 26240144 Paper 26086899 Paper 26079694 Paper 26048679 Paper 25972361 Paper 25791316 Paper 25637755 Paper 25625804 Paper 25453714 Paper 25422968 Paper 25325994 Paper 25258648 Paper 25064045 Paper 24932473 Paper 24866556 Paper 24635549 Paper 24602036 Paper 24558237 Paper 24372468 Paper 24288542 Paper 24262718 Paper 24239431 Paper 24174578 Paper 24155779 Paper 24144001 Paper 24002798 Paper 23980110 Paper 23920223 Paper 23814095 Paper 23793474 Paper 23733406 Paper 23732482 Paper 23703818 Paper 23667715 Paper 23606237 Paper 23504347 Paper 23395953 Paper 23380312 Paper 23303812 Paper 23212919 Paper 23133440 Paper 23098696 Paper 23059060 Paper 23012315 Paper 22980907 Paper 22889612 Paper 22875976 Paper 22858210 Paper 22850736 Paper 22808206 Paper 22748181 Paper 22714686 Paper 22632594 Paper 22629115 Paper 22537725 Paper 22537357 Paper 22459791 Paper 22408251 Paper 22374506 Paper 22302692 Paper 22302246 Paper 22287998 Paper 22227318 Paper 22158829 Paper 22102300 Paper 22096007 Paper 21987461 Paper 21915303 Paper 21804758 Paper 21796371 Paper 21768204 Paper 21715688 Paper 21705339 Paper 21668365 Paper 21621145 Paper 21613400 Paper 21605664 Paper 21559738 Paper 21556277 Paper 21499436 Paper 21486221 Paper 21414103

Abstract

EXCEED THE SPACE PROVIDED. Ovarian cancer is the leadingcause of death among gynecologic cancers in the United States. The prostaglandin (PG) pathway mediated by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes is implicated in ovulation and has been suggested as a potential factor in the etiology of ovarian cancer. Preliminary Data: We have utilized cDNA microarrays to compare normal ovarian tissue samples to ovarian carcinomas, and through this process have shown expression levels of COX-1 to be more than 2-fold higher in the cancers. Data published by our collaborators similarly demonstrates that COX-1, not COX-2, is highly expressed in ovarian malignancies. Hypothesis and Aims: The long-range goal of this research is to determine the specific contributions of COX-1 to ovarian carcinogenesis. We hypothesize that in ovarian cancers, COX-1 induces PGE2 production, which targets phosphatidylinositol3 kinase/protein kinase B (PI3K/AKT) signaling and components of this pathway that are involved in tumor growth and progression. We propose the use of custom-made tissue arrays for immunohistochemistry(IHC) staining to measure expression levels of COX-1, COX-2 and molecular markers associated with PI3K: phosphorylated AKT (pAKT), hypoxia induced factor (HIF-la) and vascular endothelial growth factor (VEGF). Parallel in vitro experiments will be performed to further evaluate COX-1 function by treating a COX-1 expressing cell line, OVCAR3, with a selective COX-1 inhibitor,SC-560. We will measure PGE2 metabolism, cell growth, apoptosis, migrationand invasion, as well as expression levels of PI3K, pAKT, HIF-la and VEGF. We will also utilize cDNA microarrays to generate gene profiles that are associated with COX-1. Significance: If we determine that COX-1 is indeed a prominent factor in rumor progression in ovarian cancer, this research may provide the basis for its future use as a biomarker and target for therapy in the management of this deadly disease.

View original record on NIH RePORTER →