PAR, a novel androgen regulated gene, ubiquitously expressed in normal and malignant cells.
During our work on the mechanism of hormone resistance of prostatic carcinomas, a novel gene that we called PAR (prostate androgen regulated) was isolated from an androgen resistant subline (LNCaP-OM) using a modified representational difference analysis. The complete sequence of the gene cDNA has 1029 nucleotides with a continuous reading frame of 438 bases encoding for 146 amino acids. Its deduced amino acid sequence has motifs for myristoylation 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 was higher in androgen resistant prostate cancer lines DU145, PC3 and LNCaP-OM, 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 all 29 normal human tissues studied and overexpressed in most (67%) of their malignant counterparts. The PAR expression was higher in MCF7 and T47D breast cancer cell lines, as well as in all primary breast tumors studied compared to their normal tissue counterparts. The biological function of this gene is still unknown, but its ubiquitous expression in normal tissues and its overexpression in some malignancies suggest the PAR involvement in certain basic cellular processes and possibly, in malignant transformation.
Platica
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Department of Medicine, Health Science Center at Brooklyn, SUNY and VA Medical Center, Brooklyn, NY 11209, USA.
Chen
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Ivan
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Lopingco
M C
MC
Holland
J F
JF
Platica
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D000595:Amino Acid Sequence; D000728:Androgens / Q000494:pharmacology*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D002460:Cell Line; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; C407989:JTB protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins