Up-regulated expression of the MAT-8 gene in prostate cancer and its siRNA-mediated inhibition of expression induces a decrease in proliferation of human prostate carcinoma cells

Abstract

In order to analyze differential gene expression of putative prostate tumor markers we compared the expression levels of >400 cancer-related genes using the cDNA array technique in a set of prostate tumors and matched normal prostate tissues. Up-regulated expression of mammary tumor 8 kDa protein (MAT-8), complement component C1S (C1S), ferritin heavy chain (FTH1), peptidyl-prolyl cis-trans isomerase A (PPIA), RNA-binding protein regulatory subunit DJ-1 protein (DJ-1) and vacuolar ATP synthase subunit F (ATP6V1F) was determined in prostate carcinoma and confirmed by using quantitative real-time RT-PCR analyses. Furthermore, quantitative real time RT-PCR on intact RNAs from 11 paired laser microdissected epithelial tissue samples confirmed up-regulated MAT-8 expression in 6 out of 11 prostate tumors. To determine the function of MAT-8 in vitro, human PC-3 and LNCaP prostate carcinoma cells were transfected with small interfering double-stranded RNA (siRNA) oligonucleotides against the MAT-8 gene leading to a specific down-regulation of MAT-8 expression. In addition, suppression of MAT-8 expression caused a significant decrease in cellular proliferation of both prostate cancer cell lines, whereas invasive capacity and cellular apoptosis remained unaffected. Taken together, our results indicate that the human MAT-8 gene contains the potential to serve as a prostate cancer expression marker and that MAT-8 plays an important role in cellular growth of prostate carcinomas.