Prostatic androgen repressed message-1 (PARM-1) may play a role in prostatic cell immortalisation

BACKGROUND. Prostatic androgen-repressed message-1 (PARM-1) has been cloned from the prostate. The transcript of the PARM-1 gene is overexpressed during regression of the prostate after androgen withdrawal. The regulation of PARM-1 by androgens is limited to this organ. We have studied the effects of PARM-1 overexpression in malignant prostate cells. METHODS. The PARM-1 cDNA was introduced into the rat cancer cell line MAT LyLu along with a doxycycline-dependent regulator. RESULTS. Maximal expression of PARM-1 (fivefold induction) was achieved by incubating the cells with 2 muM doxycycline for 48 hr. A study investigating the effect of PARM-1 overexpression on the transcription of 588 genes has shown that the TLP1 gene (encoding rat telomerase protein component 1) was the most up-regulated (fourfold). In addition, a dose-dependent increase in telomerase activity was observed in cells overexpressing PARM-1. In vivo, the androgen-deprived prostate showed an increased TLP1 level and increased telomerase activity. CONCLUSIONS. Increased telomerase activity is often associated with the immortalisation of cancer cell lines, particularly prostatic ones. This could mean that PARM-1 is involved, via increased telomerase activity, in a survival program enabling certain prostatic cells to resist apoptosis, thus conferring a selective advantage to pre-cancerous or cancerous cells. (C) 2003 Wiley-Liss, Inc.