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 microM 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.
Copyright 2003 Wiley-Liss, Inc.