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Growth Inhibition of Prostate Cancer by an Adenovirus Expressing a Novel Tumor Suppressor Gene, pHyde¹

University of Tennessee Urologic Research Laboratories, Department of Urology, University of Tennessee-Memphis [M. S. S., X. Z., Y. W., Y. L.], and Genotherapeutics, Inc., [M. S. S., Y. L.] Memphis, Tennessee 38163

It has been estimated that there will be >180,400 new cases of prostate cancer and 31,900 prostate cancer deaths in the United States this year. New therapeutic strategies against locally advanced prostate cancer are desperately needed. A novel gene (pHyde) was identified by an improved cDNA competition hybridization technique for Dunning rat prostate cancer cell lines. A recombinant replication-deficient E1/E3-deleted adenovirus type 5 containing a pHyde gene under the control of a truncated Rous sarcoma virus (RSV) promoter (AdRSVpHyde) was generated. In vitro, AdRSVpHyde significantly inhibited growth of human prostate cancer cell lines DU145 and LNCaP in culture. In vivo, a single injection of AdRSVpHyde (5 x 10⁹ plaque-forming units) reduced DU145 tumors in nude mice remarkably compared with untreated control or viral control-treated DU145 tumors. Moreover, AdRSVpHyde induced apoptosis and stimulated p53 expression. These results together suggest that pHyde is a tumor suppressor gene that inhibits growth of prostate cancer and that this inhibition is at least in part due to the induction of apoptosis.

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