New Genomic Structure for Prostate Cancer Specific Gene PCA3 within BMCC1: Implications for Prostate Cancer Detection and Progression

Authors

Raymond A. Clarke, University of New South Wales
Zhongming Zhao, Virginia Commonwealth UniversityFollow
An-Yuan Guo, Virginia Commonwealth University
Kathrein Roper, Stanford University
Linda Teng, Queensland Institute of Medical Research
Zhi-Ming Fang, Queensland Institute of Medical Research
Hema Samaratunga, Sullivan & Nicolaides Pathology
Martin F. Lavin, Queensland Institute of Medical Research
Robert A. Gardiner, University of Queensland Centre for Clinical Research

Document Type

Article

Original Publication Date

2009

Journal/Book/Conference Title

PLOS ONE

Volume

4

DOI of Original Publication

10.1371/journal.pone.0004995

Comments

Originally Published at : http://dx.doi.org/10.1371/journal.pone.0004995

Date of Submission

November 2014

Abstract

Background

The prostate cancer antigen 3 (PCA3/DD3) gene is a highly specific biomarker upregulated in prostate cancer (PCa). In order to understand the importance of PCA3 in PCa we investigated the organization and evolution of the PCA3 gene locus.

Methods/Principal Findings

We have employed cDNA synthesis, RTPCR and DNA sequencing to identify 4 new transcription start sites, 4 polyadenylation sites and 2 new differentially spliced exons in an extended form of PCA3. Primers designed from these novel PCA3 exons greatly improve RT-PCR based discrimination between PCa, PCa metastases and BPH specimens. Comparative genomic analyses demonstrated that PCA3 has only recently evolved in an anti-sense orientation within a second gene, BMCC1/PRUNE2. BMCC1 has been shown previously to interact with RhoA and RhoC, determinants of cellular transformation and metastasis, respectively. Using RT-PCR we demonstrated that the longer BMCC1-1 isoform - like PCA3 – is upregulated in PCa tissues and metastases and in PCa cell lines. Furthermore PCA3 andBMCC1-1 levels are responsive to dihydrotestosterone treatment.

Conclusions/Significance

Upregulation of two new PCA3 isoforms in PCa tissues improves discrimination between PCa and BPH. The functional relevance of this specificity is now of particular interest given PCA3'soverlapping association with a second gene BMCC1, a regulator of Rho signalling. Upregulation of PCA3 and BMCC1 in PCa has potential for improved diagnosis.

Rights

Copyright: © 2009 Lavin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Psychiatry Publications