Estrogens, Microtubules and Aneuploidy: Mechanisms of Mammary Gland Tumorigenesis.
Annual rept. 15 Jun 98-14 Jun 99
KANSAS UNIV MEDICAL CENTER KANSAS CITY
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Final characterization of the oxidation of estradiol E2 by rat liver microsomal RLM preparations from ACI and Sprague-Dawley rats has shown that 4-hydroxy-E2 is the major product in the ACI RLM. This product is virtually undetectable in incubations using Sprague-Dawley RLM, where 2-hydroxy-E2 is the major product. Western immunoblotting showed that RLM from both strains contained comparable amounts of CYP 2B12 and or 3A12, but not detectable CYP 1A12. Also, neither strain expressed detectable amounts of CYP 1B1. Although this enzyme is not considered to be a constitutive CYP in rat liver, its presence in the ACI RLM would provide a ready explanation for the predominance of 4-hydroxy-E2 as a product. The identity of the estradiol 4-hydroxylase in the ACI RLM remains to be elucidated. Studies with primary mammary epithelial cells from the two strains have centered on the effects of E2 on overall proliferative rates, and in particular on the effects of E2 on the relative numbers of myoepithelial and lumenal and alveolar epithelial cells. These are key insights required for the design and performance of the studies on microtubule integrity and induction of aneuploidy to be performed next.
- Anatomy and Physiology
- Medicine and Medical Research