Nov 15, 2011

Effects of estrogen metabolite 2-methoxyestradiol on tumor suppressor protein p53 and proliferation of breast cancer cells

Systems Biology in Reproductive Medicine
Amy E SiebertVirinder Moudgil

Abstract

An endogenous 17β-estradiol (E(2)) metabolite, 2-methoxyestradiol (2-ME(2)), has been reported to exhibit estrogen receptor (ER)-independent anti-angiogenic and anti-tumor effects. Several mechanisms have been proposed for 2-ME(2) actions, but there is a lack of evidence for a common pathway for all of the cell-types sensitive to this metabolite. We have examined potential alterations in p53 in response to 2-ME(2), E(2) and the microtubule disruptor taxol in T47D breast cancer cells. Cells were cultured for six days in medium depleted of endogenous steroids or effectors. Semi-confluent cells were treated with 2-ME(2) (1 nM - 10 µM), 10 nM E(2) and/or 1 µM taxol and subjected to SDS-PAGE and Western blot analysis, quantitative analysis, or laser-scanning confocal microscopy. Western blot analysis revealed a concentration-dependent biphasic trend in p53 levels. Addition of 10 nM - 1 µM 2-ME(2) induced significant up-regulation in p53, and this response gradually diminished to levels comparable to the control upon treatment with higher concentrations (2.5 - 10 µM). The observed upregulation of p53 induced by 2-ME(2) is inhibited by concurrent treatment with 1 µM taxol. Cell quantitation revealed a significant decrease (50 - 90%) i...Continue Reading

Mentioned in this Paper

SDS-PAGE
Panzem
Estradiol, (16 alpha,17 beta)-Isomer
Cell Proliferation
ESR1 gene
Western Blot
Protein p53
Estradiol
Metabolite
Taxol

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