Recombinant adenovirus vector expressing wild-type p53 is a potent inhibitor of prostate cancer cell proliferation.
OBJECTIVE
A recombinant adenovirus vector (AdWTp53) expressing wild-type p53 was evaluated for its cell growth inhibitory effects on metastatic human prostate cancer cells.


METHODS
Human prostate cancer cells LNCaP, DU145, PC3, 1LN, and DUPro-1 were infected with AdWTp53 vector and expression of exogenous p53 in these cells was analyzed by immunoprecipitation and western blot assays. The cell growth inhibitory effects of AdWTp53 were determined by counting cell number on a hemocytometer or by crystal violet staining of cells after infection with AdWTp53. The p53-regulated gene WAF1 and DNA fragmentation were also analyzed in prostate cancer cells infected with AdWTp53.


RESULTS
High levels of the AdWTp53 vector-derived p53 protein were present in metastatic prostate cancer cells, and the p53-regulated gene WAF1 was induced in these cells. Infection of these tumor cell lines with AdWTp53 vector resulted in severe growth inhibition and cell death in comparison to untreated or control adenovirus vector-infected cells. Furthermore, fragmentation of genomic DNA, a property associated with apoptosis, was also observed in prostate cancer cells infected with AdWTp53.


CONCLUSIONS
AdWTp53 vector exhibited a potent inhibitory effect on the growth of all of human metastatic prostate cancer cells, and both cytostatic and cytotoxic effects of AdWTp53 were observed. The induction of p53-regulated gene WAF1 in AdWTp53-infected prostate cancer cells suggests the involvement of cellular p53 pathway in the cell growth inhibition. These results provide a molecular basis for further evaluation of antitumorigenic effects of AdWTp53 vector in animal models of prostate cancer.
Srivastava
S
S
Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
Katayose
D
D
Tong
Y A
YA
Craig
C R
CR
McLeod
D G
DG
Moul
J W
JW
Cowan
K H
KH
Seth
P
P
D000260:Adenoviruses, Human / Q000235:genetics*; D015153:Blotting, Western; D002455:Cell Division; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008297:Male; D011233:Precipitin Tests; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53