STUDIES ON THE MOLECULAR MECHANISM OF GROWTH-INHIBITION WITH P53 ADENOVIRAL CONSTRUCT IN HUMAN OVARIAN-CANCER

Citation
K. Mujoo et al., STUDIES ON THE MOLECULAR MECHANISM OF GROWTH-INHIBITION WITH P53 ADENOVIRAL CONSTRUCT IN HUMAN OVARIAN-CANCER, International journal of gynecological cancer, 8(3), 1998, pp. 233-241
Citations number
28
Categorie Soggetti
Obsetric & Gynecology",Oncology
ISSN journal
1048891X
Volume
8
Issue
3
Year of publication
1998
Pages
233 - 241
Database
ISI
SICI code
1048-891X(1998)8:3<233:SOTMMO>2.0.ZU;2-T
Abstract
Advanced stage human ovarian cancer exhibits 50-60% mutation of the p5 3 tumor suppressor gene. We introduced the wild-type p53 gene into the cells using a replication deficient recombinant adenovirus for p53 ge ne therapy. p53-adenovirus (rAd-p53) inhibited the growth of a number of ovarian cancer cells, which correlated well with the transduction o f adenovirus containing beta-galactosidase reporter gene in the tested cell lines. Results presented herein demonstrate that p53 induced the expression of CDK inhibitor WAF1/CIP1/p21 in human ovarian cancer cel ls with null or mutant p53. p53 incorporation also induced the express ion of mdm-2 and bar proteins in human ovarian cancer cells. In contra st, we were unable to detect the expression of bcl-2 protein in the te sted cells, and the expression bcl-x, in the tested human ovarian cell s was not altered post-infection of cells with rAd-p53. Cell cycle ana lysis revealed pronounced G1 arrest 24 h post-infection with rAd-p53 i n human ovarian cancer cells with only a small percentage of cells (si milar to 2%) undergoing apoptosis. rAd-p53 (p53-adenovirus) inhibited the growth of established subcutaneous xenograft tumors (OVCAR-3) of h uman ovarian carcinoma and completely regressed the tumors in 5/8 mice , indicating a potential for p53 tumor suppressor gene therapy in huma n ovarian cancer.