title: New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression.
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.
  
  
  RESULTS
  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 and BMCC1-1 levels are responsive to dihydrotestosterone treatment.
  
  
  CONCLUSIONS
  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's overlapping association with a second gene BMCC1, a regulator of Rho signalling. Upregulation of PCA3 and BMCC1 in PCa has potential for improved diagnosis.
authors.affiliation: Prostate Cancer Institute, Cancer Care Centre, St George Hospital Clinical School of Medicine, University of New South Wales, Kogarah, New South Wales, Australia.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Clarke
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: An-Yuan
authors.initials: AY
authors.lastname: Guo
authors.forename: Kathrein
authors.initials: K
authors.lastname: Roper
authors.forename: Linda
authors.initials: L
authors.lastname: Teng
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Fang
authors.forename: Hema
authors.initials: H
authors.lastname: Samaratunga
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gardiner