Adenovirus-mediated Expression of PML Suppresses Growth and Tumorigenicity of Prostate Cancer Cells
[CANCERRESEARCH57. 1868-1872. May 15.1997]，-0001，（）：
Our previous studies demonstrated that the promyelocytic leukemia gene, PML,encodes a growth and transformation suppressor. Overexpres sion of PML inhibits cancer cell growth in vitroand in vivo. In this study, we further explored the possibility of applying PML as a potential agent for developing prostate cancer gene therapy using an adenovirus delivery system. We have constructed and produced the recombinant PML-ade novirus, Ad-PML, in which the full-length PML eDNA is driven by the strong cytomegalovirus promoter. In LNCaP, DU145, and PC-3 prostate cancer cell lines, an infection efficiency of 90% can be achieved at a concentration of 2, 10, and 100 multiplicity of infection (MOl), respec tively. Western blotting and immunofluorescence staining demonstrated that the AD-PML-infected cells expressed a high level of PML protein. The protein expression peaked at days 3â€”4postinfection, and a detectable level of PML was found at day 18 after viral infection. To test the effect of Ad-PML on the growth of prostate cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MOl of Ad-PML. We found that the growth rate of the Ad-PML-infected DU145 and LNCaP cells were sig nificantly inhibited. A tumorigenicity test in nude mice showed that the Ad-PML-treated DU145 cells failed to form tumors. Most importantly, direct injection of Ad-PML into DU145-induced tumors was able to repress tumor growth in nude mice by 64%. Taken together, these data indicate that PML is a tumor growth suppressor in prostate cancer and that Ad-PML may be a potential candidate for human prostate cancer therapy.
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