Graduate student Amy Siebert publishes paper on breast cancer

In 1993 Science Magazine named p53 its “Molecule of the Year” because of its ability to suppress tumors in humans. The development of many breast cancers is affected by hormones such as estrogen, so it is natural to ask if these hormones act by increasing the amount of p53. Graduate student Amy Siebert, in the Master of Science in Biology program, was lead author on a paper about “Effects of Estrogen Metabolite 2-Methoxyestradiol on Tumor Suppressor Protein p53 and Proliferation of Breast Cancer Cells,” published in the December issue of the journal Systems Biology in Reproductive Medicine (Volume 57, Pages 279-287). Coauthors include graduate student Amy Sanchez in the Biomedical Sciences: Biological Communication PhD program, Assistant Professor Sumi Dinda of the School of Health Sciences, and Professor Virinder Moudgil, of the Department of Biological Sciences, who is Oakland University’s Senior Vice President for Academic Affairs and Provost. The abstract of Siebert’s paper is given below.

An endogenous 17 beta-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 mu M), 10 nM E(2) and/or 1 mu M 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 mu M 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 mu M). The observed upregulation of p53 induced by 2-ME(2) is inhibited by concurrent treatment with 1 mu M taxol. Cell quantitation revealed a significant decrease (50 - 90%) in cell number upon treatment with 1 - 10 mu M 2-ME(2) with minimal effect at lower concentrations. No additional effect on cell proliferation was observed when taxol was combined with 10 nM or 1 mu M 2-ME(2). In a concentration dependent manner, treatment with 2-ME(2) for 24 h differentially influenced cellular localization of p53. These results may aid in further understanding the relationship between steroid receptors, tumor suppressor proteins, and effects of hormone metabolites on breast cancer cells.