Cell cycle regulatory protein expression profiles by adenovirus p53 infection in human papilloma virus-associated cervical cancer cells.
OBJECTIVE
The tumor suppressor gene, p53, has been established as an essential component for the suppression of tumor cell growth. In this study, we investigated the time-course anticancer effects of adenoviral p53 (Adp53) infection on human ovarian cancer cells to provide insight into the molecular-level understanding of the growth suppression mechanisms involved in Adp53-mediated apoptosis and cell cycle arrest.


METHODS
Three human cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of Adp53 infection was studied via cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay.


RESULTS
Adp53 exerts a significant role in suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53 differentially regulated the expression of genes and proteins, and the gene expression profiles in the SiHa cells revealed that the p21, p53 and mdm2 expressions were significantly up-regulated at 24 and 48 hr. Western blot shows that the p21 and p53 expression-levels were significantly increased after Adp53 infection. In addition, in all cell lines, both the CDK4 and PCNA protein expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at the G1 phase was induced only in the SiHa and HeLa cells, suggesting that exogenous infection of Adp53 in cancer cells was significantly different from the other HPV-associated cervical cancer cells.


CONCLUSIONS
Adp53 can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest, as well as through the regulation of the cell cycle-related proteins. The Adp53-mediated apoptosis can be employed as an advanced strategy for developing preferential tumor cell-specific delivery.
Lee
Yong-Seok
YS
Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Bae
Su-Mi
SM
Kwak
Sun-Young
SY
Park
Dong-Chun
DC
Kim
Yong-Wook
YW
Hur
Soo-Young
SY
Park
Eun-Kyung
EK
Han
Byoung-Don
BD
Lee
Young-Joo
YJ
Kim
Chong-Kook
CK
Kim
Do Kang
DK
Ahn
Woong-Shick
WS