Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Dianzheng Zhang, PhD

Second Advisor

Ruth C. Borghaei, PhD

Third Advisor

Marina D’Angelo, PhD

Fourth Advisor

Marcus Bell, PhD

Abstract

The chemopreventive effects of resveratrol (RSV) on cancers, including prostate cancer, have been well documented; but the mechanisms are not well known. It has been reported recently that tensin, a matrix-adhesion protein, which is greatly down-regulated in prostate cancer, has been induced by RSV in several cancer cell lines. In order to know if RSV up-regulates tensin in prostate cells, we first treated LNCaP cells with RSV and demonstrated that tensin mRNA levels were upregulated by RSV in a time and dose dependent manner. Since LNCaP cells are androgen receptor (AR) positive and previous findings have shown that RSV down-regulates AR protein levels as well as its transcriptional activity, we were interested to see whether RSV effects on tensin are AR dependent. When LNCaP cells were treated with androgen (R1881), tensin mRNA levels were down-regulated and this effect was counteracted by RSV. These results strongly suggest that RSV upregulation of tensin mRNA at least partially involves AR. To further confirm its AR dependency, we used a previously established stable AR(+) expressing HeLa cell line in a series of experiments; with the AR(-) HeLa cell line serving as a negative control. Similar to what we saw in LNCaP cells, tensin mRNA levels were upregulated in the AR(+) cells, and RSV counteracted androgen induced downregualtion of tensin mRNA levels. However, this effect was not shown in the AR(-) cells. In summary, we have demonstrated that RSV up-regulates tensin expression in prostate cancer cells and this effect is, at least in part, AR dependent. Together with our previous observations, we provided further evidence at both cellular and molecular levels that RSV may serve as a preventative and therapeutic agent for prostate cancer.

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