PAR, a novel androgen regulated gene, ubiquitously expressed in normal andmalignant cells

During our work on the mechanism of hormone resistance of prostatic carcino mas, a novel gene that we called PAR (prostate androgen regulated) was isol ated from an androgen resistant subline (LNCaP-OM) using a modified represe ntational difference analysis. The complete sequence of the gene cDNA has 1 029 nucleotides with a continuous reading frame of 438 bases encoding for 1 46 amino acids. Its deduced amino acid sequence has motifs for myristoylati on and phosphorylation by protein kinase C. The PAR gene was overexpressed in all prostatic carcinoma cell lines studied (LNCaP, DU145, PC3 and LNCaP- OM) compared to the normal prostatic tissue. Furthermore, its expression wa s higher in androgen resistant prostate cancer lines DU145, PC3 and LNCaP-O M, in comparison to androgen sensitive LNCaP cells. The expression of this gene was down regulated by androgens in androgen sensitive prostate cells, but not in the hormone resistant cell lines. The PAR mRNA was detected in a ll 29 normal human tissues studied and overexpressed in most (67%) of their malignant counterparts. The PAR expression was higher in MCF7 and T47D bre ast cancer cell lines, as well as in all primary breast tumors studied comp ared to their normal tissue counterparts. The biological function of this g ene is still unknown, but its ubiquitous expression in normal tissues and i ts overexpression in some malignancies suggest the PAR involvement in certa in basic cellular processes and possibly, in malignant transformation.