Poster abstracts

Poster number 101 submitted by Narmada Pandey Sapkota

AR Precursor mRNA Splicing: Understanding the Cause and Consequence of Drug Resistance in Prostate Cancer

Narmada Pandey Sapkota (BGES, Cleveland State University), Jey Sabith Ebron (BGES, Cleveland State University), Girish C Shukla, Ph.D. (BGES, Cleveland State University)

Abstract:
Prostate cancer is the most prevalent cancer in American male and only second to skin cancer. Progression of prostate cancer mainly depends on expression and signaling of androgen receptor (AR). AR is a ligand-dependent transcription factor of steroid receptor family, which is required for normal growth and development. It plays a pivotal role in development of prostate cancer. Conventional treatment for the prostate cancer mainly involves androgen deprivation, surgical or medical castration. Nearly 20% of prostate cancer either bypass or sensitize the AR signaling pathway leading to an advanced form of disease, castration resistance prostate cancer (CRPC). Among many molecular mechanism involving AR functions in development of CRPC, expression of novel alternative spliced isoform appears to play an important role. Various, alternatively spliced, AR isoforms have been identified in prostate cancer, however molecular mechanism contributing to the expression of these novel tumors-specific isoforms and their function remains undefined. In this study, we are investigating AR precursor mRNA splicing in an attempt to understand the development of drug resistance, presumably mediated by novel AR mRNA alternatively spliced isoforms in prostate cancer. We are planning to study the effect of AR mutations on AR pre-mRNA splicing using a novel AR minigene reporter construct. Our experiment aims to reveal the consequences of naturally occurring mutations of AR in prostate cancer patients, who have developed resistance to next generation of therapeutics including Enzalutamide (Xtendi) and Abiraterone Acetate (Zytiga). We will discuss the preliminary data obtained from initial AR minigene splicing characterization experiment. Understanding the basic molecular mechanism of alternative splicing of AR in prostate cancer will help better management of prostate cancer.

Keywords: AR Splicing, AR precursor mRNA splicing