Role of Estrogen Metabolism in the Initiation of Prostate Cancer: Biomarkers of Susceptibility and Early Detection
Abstract
Treatment of Noble rats with testosterone plus estradiol (E2) induces prostate carcinomas. We think that estrogens initiate prostate cancer by reaction of catechol estrogen-3,4-quinone (CE-3,4-Q) metabolites with DNA. Formation of depurinating adducts by CE-3,4-Q, which generate apurinic sites in DNA, would be the critical event leading to mutations that initiate prostate cancer. After treatment of rats with CE or CE-3,4-Q, CE metabolites and CE-glutathione (GSH) conjugates were lower in regions where tumors develop and methoxyCE were higher in regions where tumors do not develop. To study the role of CE-Q in initiation of prostate cancer, we are (1) treating rats with E2 and/or testosterone and analyzing the CE metabolites, CE-GSH conjugates and depurinating CE-DNA adducts in the regions of the prostate by HPLC with electrochemical and mass spectrometric detection; (2) studying in the prostate conversion of testosterone into E2 and its metabolism; and (3) determining the expression at the mRNA level of four selected enzymes involved in estrogen activation and deactivation in the prostate of rats treated with E2 and/or testosterone. These studies will provide information critical to understanding the molecular etiology of prostate cancer, identify biomarkers for early detection of susceptibility and lead to development of strategies for prostate cancer prevention.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2006
- Accession Number
- ADA459745
Entities
People
- Ercole L. Cavalieri
Organizations
- University of Nebraska Medical Center