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
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.