2006 Ohio Student Research Forum

Abstract

Increasing Androgen Receptor Transcriptional Activity Leads to Increased Androgen- Independent Cell Growth in Prostate Cancer
Aaronica Bivins
University of Toledo
Department of Biological Sciences
Mentor(s): Dr. Lirim Shemshedini

Androgens function by binding to androgen receptor (AR), which regulates gene expression. AR and androgens play a key role in the progression of prostate cancer as it transitions from an androgen-dependent to an independent stage. The conversion from the androgen-dependent to the independent stage can be caused by the over-expression of AR, which leads to elevated AR-regulated gene expression. To reproduce this effect in a novel way, we attempted to increase AR transcriptional activity by fusing the VP16 transcriptional activator to AR. Several LNCaP stable cell lines were generated expressing VP16-AR, which exhibited AR transcriptional activity that was 3-40-fold greater than LNCaP cells expressing native AR. One VP16-AR cell line was studied for androgen-induced cell proliferation. This cell line, which has a seven-fold higher AR transcriptional activity than control LNCaP cells, yielded significantly higher androgen-independent growth than control cells. Interestingly, this VP16-AR cell line also exhibited androgen-independent expression of sGCa1, a novel androgen-regulated gene that is involved in prostate cancer cell proliferation. siRNA was used to demonstrate sGCa1 involvement in the growth of VP16-AR cells. These data show that expression of a hyperactive AR protein is sufficient for converting prostate cancer cell growth from androgen-dependent to androgen-independent.