Aberrant expression of the PRAC gene in prostate cancer

Int J Oncol. 2013 Dec;43(6):1960-6. doi: 10.3892/ijo.2013.2117. Epub 2013 Oct 2.

Abstract

Identification of aberrant expression patterns of genes in prostate cancer (PCa) is a key step towards the development of effective therapies. Prostate-specific antigen (PSA) levels are commonly measured for the early detection of PCa, but which itself is still not an ideal biomarker. We analysed the expression patterns of prostate cancer susceptibility candidate (PRAC) in prostate cancer. The PRAC gene is known to be commonly expressed in prostate tissue, rectum and colon. To provide clear insights into the expression patterns of PRAC in PCa, we examined the gene expression by quantitative real-time PCR (qRT-PCR), western blot analysis and immunohistochemistry (IHC). The results showed that PRAC expression levels in androgen‑insensitive cells (DU145 and PC3) are lower than those in androgen-sensitive cell lines (LNCaP, LNCaP-R and CW22R). However, treatment of the LNCaP cell line with androgen and anti-androgen demonstrated that PRAC is expressed in an androgen-independent manner. Further, PRAC expression was restored upon treatment of DU145 and PC3 cells with the methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-CdR), which indicates the effect of methylation in the control of PRAC expression. In addition, IHC analysis revealed a significantly decreased immunoreactivity of PRAC protein in PCa tissues compared to benign prostatic hyperplasia (BPH) (p<0.0001). Thus, our findings suggest that the pathogenesis of PCa may be due to the expression levels of PRAC protein, and this protein can serve as a potential biomarker for the management of PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology
  • Androgens / pharmacology
  • Antimetabolites, Antineoplastic / pharmacology
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Decitabine
  • Dihydrotestosterone / pharmacology
  • Flutamide / pharmacology
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*

Substances

  • Androgen Antagonists
  • Androgens
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Nuclear Proteins
  • PRAC1 protein, human
  • Dihydrotestosterone
  • Flutamide
  • Decitabine
  • Azacitidine