Identification and Characterization of a Novel Testosterone-Regulated Prominin-Like Gene in the Rat Ventral Prostate

Abstract

More than two dozen androgen-responsive genes were identified from the castrated rat ventral prostate on the basis of their induction by exogenous testosterone. One of the identified genes encodes a novel 886-amino-acid protein that was named prominin-like protein 2 (PROML2) because it shares 32% identity to prominin and prominin-like protein 1, a family of important plasma membrane proteins with five transmembrane domains. The rat PROML2 gene is expressed abundantly in the glandular epithelial cells of the rat ventral prostate. The PROML2 gene is expressed in the human prostate and human prostate cancer cell lines with the highest level in less aggressive LNCaP cells and low expression in highly aggressive PC3 and DU145 cells, suggesting a correlation between PROML2 down-regulation and aggressiveness of prostate cancer cells. Transient transfection of green fluorescent protein-tagged rat PROML2 expression vector into prostate cancer cell lines showed that PROML2 protein is localized to the nuclear envelope and perinuclear region and induces cell death in all of the transfected prostate cancer cells. Taken together, our results argue that PROML2 is a novel proapoptotic membrane protein and its down-regulation may associate with aggressive phenotype of prostate cancer cells.

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

“…Consistently, among the prostatic carcinoma cells of human origin commonly studied, e.g. DU145, PC3 and LNCaP, only the latter showed good expression of Prominin-2 as assessed by PCR (Zhang et al 2002). Inasmuch as these prostate cancer cells predominantly display more luminal, secretory-like phenotypes this might indicate that the diVerentiation grade of the prostate tumors could negatively correlate with PROMININ-2 expression.…”

“…DiVerential gene expression studies revealed that a number of basal cell markers were expressed as well by cancer cells especially by those that were poorly diVerentiated (McDonnell et al 1992;Liu et al 1996). Expression of Prominin-2, however, was hardly detectable by northern blot in prostate cancer cells (Zhang et al 2002). Consistently, among the prostatic carcinoma cells of human origin commonly studied, e.g.…”

“…2E, F, tm). The expression of Prominin-2 in the prostate was Wrst described in rats as an androgen responsive gene (Zhang et al 2002). Analyzing its expression in the murine ventral prostate we have observed that the signal, was conWned to the glandular epithelial cells (Fig.…”

“…It is of note that the expression of PROMININ-2 in the human prostate is restricted to basal cells, which are androgen receptor (AR) negative or expressing it at very low level, given that the rat orthologue was Wrst reported as a testosterone-regulated gene (Zhang et al 2002). In fact, testosterone deprivation in the rodent castration model decreased Prominin-2 expression, and hormone replacement restored it.…”

“…Prominin-2 seems to be particularly enriched in the rat prostate, where it was described as a novel prominin-like protein encoded by an androgen-responsive gene in the ventral prostate (Zhang et al 2002). Similarly, expression of PROMININ-2 in the human prostate and prostate cancer cell lines of human origin was also demonstrated on tissue-speciWc Northern blots (Zhang et al 2002;Fargeas et al 2003a). In contrast, PROMININ-1 (i.e.…”