ADENOVIRUS-MEDIATED EXPRESSION OF PML SUPPRESSES GROWTH AND TUMORIGENICITY OF PROSTATE-CANCER CELLS

Our previous studies demonstrated that the promyelocytic leukemia gene , PML, encodes a growth and transformation suppressor, Overexpression of PML inhibits cancer cell growth in vitro and ill vivo. In this stud y, 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- adenovirus, Ad-PML, in which the full-length PML cDNA is driven by the strong cytomegalovirus promoter, In LNCaP, DU145, and PC-3 prostate c ancer cell lines, an infection efficiency of 90% can be achieved at a concentration of 2, 10, and 100 multiplicity of infection (MOI), respe ctively, 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 3-4 postinfection, and a detect able level of PML was found at day 18 after viral infection, To test t he effect of Ad-PML on the growth of prostate cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MOI of Ad-PML. We found th at the growth rate of the Ad-PML-infected DU145 and LNCaP cells were s ignificantly inhibited, A tumorigenicity test in nude mice showed that the Ad-PML-treated DU145 cells failed to form tumors, Most importantl y, direct injection of Ad-PML into DU145-induced tumors was able to re press tumor growth in nude mice by 64%, Taken together, these data ind icate that PML is a tumor growth suppressor in prostate cancer and tha t Ad-PML may be a potential candidate for human prostate cancer therap y.