Estrogens, Microtubules and Aneuploidy: Mechanisms of Mammary Gland Tumorigenesis.
Abstract
The role of estradiol (E2) metabolism in mammary carcinogenesis is being studied in a rat model. Two strains are employed: the ACI is extremely sensitive to E2 carcinogenicity, whereas the Sprague-Dawley is resistant. Characterization of E2 metabolism in liver microsomal preparations showed robust metabolism from 60 micrometerm down to 3 nM. The latter value approximates the physiological concentration of E2. In the micromolar range both strains produce estrone and 2-hydroxy-E2. In the nanomolar range, however, estrone is the dominant product from the Sprague-Dawley whereas the ACI makes almost entirely 4-hydroxy-E2. Given that 4- hydroxy-E2 may be the key carcinogenic metabolite of E2, this strain-specific metabolism may explain the noted difference in E2 carcinogenicity between the two strains. Although liver determines the systemic fate of E2, metabolism and effects of E2 in target tissues are of even more concern. Therefore, these studies will be extended to the rat mammary epithelial cell (RMEC) system. We have isolated and cultured RMEC from both rat strains. The resulting cultures are, a mixed population, containing about 65% myoepithelial cells surrounding colonies of lumenal epithelial cells. Although metabolism will provide a summation of contributions from all cell types, the studies of microtubule effects and aneuploidy will be cell-type specific.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA353862
Entities
People
- Gregory A. Reed
Organizations
- University of Kansas Medical Center