Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


osu1117117648.pdf (1.56 MB)

ETD Abstract Container

Abstract Header

Interrelationships between aromatase and cyclooxygenase-2 and their role in the autocrine and paracrine mechanisms in breast cancer

Diaz-Cruz, Edgar S
http://rave.ohiolink.edu/etdc/view?acc_num=osu1117117648

Abstract Details

2005, Doctor of Philosophy, Ohio State University, Pharmacy.
Breast cancer is the most common cancer among women, and ranks second among cancer deaths in women. Approximately 60% of all breast cancer patients have hormone-dependent breast cancer, which contains estrogen receptors and requires estrogen for tumor growth. Estradiol is biosynthesized from androgens by the cytochrome P450 enzyme complex called aromatase. Previous studies suggest a strong association between aromatase (CYP19) gene expression and the expression of cyclooxygenase (COX) genes. Our hypothesis is that higher levels of COX-2 expression result in higher levels of prostaglandin E2, which in turn increases CYP19 expression through increases in intracellular cyclic AMP levels and activation of promoter II. This biochemical mechanism may explain the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer. The effects of NSAIDs , and COX-1 and COX-2 selective inhibitors on aromatase activity and expression were studied. To determine if aromatase activity is decreased by COX inhibitors, SK-BR-3 cells were treated for 24 hours with the different concentrations of the inhibitors. The data from these experiments revealed dose-dependent decreases in aromatase activity following treatment with all agents. To measure changes in aromatase gene expression, cell cultures were treated with the inhibitors at concentrations near the IC50 values. Real time PCR analysis of aromatase gene expression showed a significant decrease in mRNA levels when compared to control for all agents. These results were consistent with enzyme activity data, suggesting that the effect of COX inhibitors on aromatase starts at the transcriptional level. To investigate which specific promoter regions are involved in this molecular mechanism, we performed exon-specific real time PCR. The results from these experiments suggest that exon I.4 and promoter II are involved in this process. Thus, prostaglandin E2 produced via COX may act locally in an autocrine fashion to increase the biosynthesis of estrogen by aromatase in hormone-dependent breast cancer development.
Robert Brueggemeier (Advisor)
243 p.
Biology, Molecular
breast cancer; nonsteroidal anti-inflammatory drugs; aromatase; cyclooxygenase

Recommended Citations

Citations

  • Diaz-Cruz, E. S. (2005). Interrelationships between aromatase and cyclooxygenase-2 and their role in the autocrine and paracrine mechanisms in breast cancer [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1117117648

    APA Style (7th edition)

  • Diaz-Cruz, Edgar. Interrelationships between aromatase and cyclooxygenase-2 and their role in the autocrine and paracrine mechanisms in breast cancer. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1117117648.

    MLA Style (8th edition)

  • Diaz-Cruz, Edgar. "Interrelationships between aromatase and cyclooxygenase-2 and their role in the autocrine and paracrine mechanisms in breast cancer." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1117117648

    Chicago Manual of Style (17th edition)

osu1117117648
1,059
© 2005, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.