Apoptosis regulators Fau and Bcl-G are down-regulated in prostate cancer.
BACKGROUND
The molecular control of cell death through apoptosis is compromised in prostate cancer cells, resulting in inappropriate cell survival and resistance to cytotoxic therapy. Reduced expression of the functionally connected apoptosis-regulators and candidate tumor suppressors Fau and Bcl-G has recently been implicated in oncogenesis in other tissues. The present study examines the hypothesis that reduced expression of these genes may be involved in prostate cancer.


METHODS
Fau and Bcl-G mRNA levels were determined by real time RT-PCR in two independent prostate tissue collections. In experiments in vitro, Fau and Bcl-G levels in prostate cancer cell lines were reduced using RNA interference and the effects on sensitivity to UVC irradiation were determined.


RESULTS
Fau and Bcl-G mRNA levels were both lower in prostate cancer tissue than in normal prostate and Benign Prostate Hyperplasia. Active down-regulation of Fau and Bcl-G expression in vitro resulted in decreased sensitivity to UVC-induced cytotoxicity. Simultaneous down-regulation of Fau and Bcl-G produced a decrease in sensitivity which was similar to either gene alone.


CONCLUSIONS
Fau and Bcl-G mRNA levels are both decreased in prostate cancer. In prostate cancer cell lines in vitro such down-regulation results in reduced sensitivity to UVC-induced cytotoxicity, consistent with the putative roles of these genes as candidate prostate tumor suppressors. The absence of an additive effect when Fau and Bcl-G were down-regulated simultaneously is consistent with the two genes acting in the same apoptosis pathway, for example, with the pro-apoptotic effects of Fau being mediated through modulation of Bcl-G.
Pickard
Mark R
MR
Institute for Science and Technology in Medicine, School of Life Sciences, Keele University, Huxley Building, Keele, UK.
Edwards
Sandra E
SE
Cooper
Colin S
CS
Williams
Gwyn T
GT
D000368:Aged; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D019940:Genes, bcl-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011467:Prostate / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics*; D014466:Ultraviolet Rays
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; C076845:FAU protein, human