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

Departments of Urology (Q.Z., R.H., X.C., Z.W.) and Molecular Pharmacology and Biological Chemistry (Z.W.), The Robert H. Lurie Comprehensive Cancer Center (Z.W.), The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611

Address all correspondence and requests for reprints to: Zhou Wang, Ph.D., Department of Urology, Tarry 11-715, Feinberg Medical School of Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611. E-mail: wangz{at}northwestern.edu.

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.

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