Growth inhibition of prostate cancer by an adenovirus expressing a novel tumor suppressor gene, pHyde.
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 10(9) 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.
Steiner
M S
MS
Department of Urology, University of Tennessee-Memphis 38163, USA.
Zhang
X
X
Wang
Y
Y
Lu
Y
Y
D017498:Adenovirus E1 Proteins / Q000235:genetics; D017503:Adenovirus E3 Proteins / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001354:Avian Leukosis Virus / Q000235:genetics; D018076:DNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007437:Intrinsic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D051381:Rats; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D017498:Adenovirus E1 Proteins; D017503:Adenovirus E3 Proteins; D018076:DNA, Complementary; D006131:Growth Inhibitors; D016159:Tumor Suppressor Protein p53; D007437:Intrinsic Factor