Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells
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Abstract
Purpose: 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. Materials and 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 expressionlevels 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. Conclusion: 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. (Cancer Res Treat. 2006;38:168-177)
참고문헌 (23)
- "Gene regulation by temperature-sensitive p53 mutants identification of p53 response genes", pp.10640~4 (1994)
- "Adenovirus-mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer", 56, pp.3047~3054 (1996)
- "Changes in p21WAF1, pRb, Mdm-2, Bax and Bcl-2 expression in cervical cancer cell lines transfected with a p53 expressing adenovirus", 36, pp.249~256 (2000)
- "Genetic determinants of p53-induced apoptosis and growth arrest", 10, pp.1945~1952 (1996)
- "Papillomaviruses as targets for cancer gene therapy", 1, pp.193~204 (1994)
- "Immortalization of primary human epithelial cells by cloned cervical carcinoma DNA containing human papillomavirus type 16 E6", E7 open reading frames, 1989;70, 1261~6
- "Biology of human papillomaviruses", 82, pp.15~33 (2001)
- "Polymorphisms of p53, p21 and IRF-1 and cervical cancer susceptibility in Korean women", 34, pp.357~364 (2002)
- "Growth inhibition of human cervical cancer cells with the recombinant adenovirus p53 in vitro", 60, pp.373~379 (1996)
- "Methods for construction of adenovirus vectors", 3, pp.207~220 (1995)
- "Enhanced tumor suppressor gene therapy via replication- deficient adenovirus vectors expressing an N-terminal truncated retinoblastoma protein", 56, pp.2245~2249 (1996)
- "Differential suppression of human cervical cancer cell growth by adenovirus delivery of p53 in vitro", 93, pp.1012~1019 (2002)
- "Anti-cancer effect of adenovirus p53 on human cervical cancer cell growth in vitro and in vivo", 14, pp.322~332 (2004)
- "Recombinant adenovirus-p53 gene transfer and cellspecific growth suppression of human cervical cancer cells in vitro and in vivo", 92, pp.611~621 (2004)
- "The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines", pp.5523~7 (1991)
- "Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1", 98, pp.859~869 (1999)
- "Apoptosis associated with deregulated E2F activity is dependent on E2F1 and Atm", Nbs1, pp.2004, 24[DOI]
- "Proliferating cell nuclear antigen immunolocalization in paraffin sections", pp.285~94 (1990)
- "E2F mediates sustained G2 arrest and down-regulation of Stathmin and AIM-1 expression in response to genotoxic stress", 278, pp.1443~1449 (2003)
- "Differences of reactivity to interferon gamma in HeLa and CaSki cells", 122(l mc), pp.223~230 (1996)
- "p53 levels, functional domains, DNA damage determine the extent of the apoptotic response of tumor cells", 10, pp.2438~2451 (1996)
- "Overexpression of the wild-type p53 gene inhibits NF-kappaB activity and synergizes with aspirin to induce apoptosis in human colon cancer cells", pp.726~36 (2000)
- "APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis", 61, pp.6660~6664 (2001)