Effect of Adenovirus-p53 to Non-Small Cell Lung Cancer Cell Lines.
- Author:
Jong Ho PARK
1
;
Chun Taek LEE
;
Joo Hyun KIM
Author Information
1. Dept. of Thoracic Surgery, Korea Cancer Center Hospital, Seoul, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Carcinoma;
non-small cell;
lung;
Gene therapy;
Adenovirus;
p53
- MeSH:
Adenoviridae;
Apoptosis;
Carcinoma, Non-Small-Cell Lung*;
Cell Death;
Cell Line*;
Genes, p53;
Genes, Tumor Suppressor;
Genetic Therapy;
Humans;
Lung;
Lung Neoplasms;
Negotiating
- From:The Korean Journal of Thoracic and Cardiovascular Surgery
1998;31(12):1134-1146
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: The tumor suppressor gene p53 is one of the most frequently altered genes in human tumors, including those of the lung. There is now a compelling evidence that wild-type p53 can negatively influence cell growth by causing G1 arrest or by inducing apoptosis. The possibilities of using p53 for gene therapy are also gathering much interest. MATERIAL AND METHOD: Our approach towards understanding p53 function would be to study the biological consequences of overexpression of wild-type p53 in normal and tumor cells by using adenovirus vectors capable of giving high levels of the p53 gene product in cells. We have used this vector containing wild-type p53 to infect tumor cells with different p53 status (null, mutant, or wild-type) to confirm that expression of p53 in null or mutant cell lines becomes possible by Adenovirus-p53 transduction, to examine the effects of high levels of p53 expression on the growth properties of tumor cells, to evaluate the role of apoptosis in p53-mediated biological effects, and to examine the effect of Adenovirus-p53 on the tumorigenicities of the lung cancer cell lines in vitro. RESULT: The results of our study showed that cells expressing endogenous mutant p53 and those devoid of p53 expression altogether were significantly more sensitive to Adenovirus-p53-mediated cytotoxicity compared to tumor cells expressing endogenous wild-type p53 and that overexpression of wild-type p53 induced programmed cell death. Also we knew that Adenovirus-p53 significantly reduced tumor colony formation of human non-small cell lung cancer cell lines, and decreased the growth of preformed colonies in vitro. CONCLUSION: These results suggest that adenovirus is an efficient vector for mediating transfer and expression of tumor suppressor genes in human non-small cell lung cancer cells and that the tumor cells null for p53 or expressing mutant p53 readily undergo apoptosis by Adenovirus-p53.
