Type 1 vasoactive intestinal peptide receptor expression in PC3/AR cells is evidence of prostate epithelial differentiation

BACKGROUND: Type 1 vasoactive intestinal peptide receptor (VIP1R) is expressed in many secretory epithelial cells. We investigated VIP1R expression as a marker of prostate secretory epithelial differentiation in normal and malignant prostate tissues and in PC-3 human prostate cancer cells either lacking or expressing a functional androgen receptor. METHODS: VIP1R mRNA in rat prostate was assessed by in situ hybridization. VIP1R mRNA in human prostate tissue was identified by Northern blot hybridization. VIP1R mRNA expression in human prostate cancer cell lines in the presence or absence of androgen was determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Human prostate cell lines were treated with VIP, and changes in intracellular cAMP were measured by radioimmunoassay. RESULTS: VIP1R mRNA was expressed only in epithelial cells in normal rat prostate. VIP1R mRNA was present in both normal and malignant human prostate. Well-differentiated LNCaP cells expressed functional VIP receptors, while poorly differentiated PC-3 cells did not. PC-3 cells stably expressing the androgen receptor (PC3/AR) did express functional VIP receptors, but VIP1R mRNA levels were not androgen-regulated. CONCLUSIONS: VIP1R expression indicates epithelial differentiation in normal and malignant prostate. PC3/AR cells and LNCaP cells, both of which express VIP1R and prostate-specific antigen (PSA), are the only prostate cancer cell lines known to express these two markers of prostate epithelial differentiation.