Proteomic Analysis of Genistein Mammary Cancer Chemoprevention
Abstract
We have hypothesized that the phytoestrogen, genistein, exerts its chemopreventive actions by postnatally programming developmental modifications to genes/proteins that render the mammary gland less susceptible to cancer. The objective of this proposed research is to identify regulatory proteins responsible for conferring breast cancer protection. The specific aims are 1)to identify proteins that are differentially expressed in mammary glands of rats treated +/- the carcinogen, DMBA, and the chemopreventive agent, genistein, and 2) to collect proteins from interstitial fluid surrounding mammary glands of rats, and to identify and characterize the major proteins that are modulated by DMBA and genistein. Using 2-D gels and mass spectrometry, we have determined that GTP-cyclohyrolase 1, a protein that plays a prominent role in the production of tetrahydrobiopterin (BH4), is modulated by genistein. BH4 is an essential co-factor for the enzyme tyrosine hyroxylase. The latter is demonstrated to be up regulated at 50 days, but not at 21 days, hence, we postulate that tyrosine hydrolase expression is regulated via a programming mechanism. Up regulated tyrosine hydroxlase is associated with increased production of dopamine, the latter has been reported to inhibit angiogenesis. Aim 2 has been initiated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA428933
Entities
People
- Coral A. Lamartiniere
Organizations
- University of Alabama