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KMID : 0869720020130010085
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Lung Research Institute
2002 Volume.13 No. 1 p.85 ~ p.91
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Adenovirus expressing p27Kip1 induces growth arrest of lung cancer cell lines and suppresses the growth of established lung cancer xenografts
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Choon Taek Lee/Kyung Ho Park
Ja Young Seol/Chul Gyu Yoo/Young Whan Kim/Sung Koo Han/Eun Ho Lee/Chang Min Kim/Young Soo Shim/Choon Taek Lee
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Abstract
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p27Kip1 (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family and a putative tumor suppressor gene. In several tumors including lung cancer, decreased expression of p27 is associated with poor prognosis. These observations suggest a potential role for p27 as a new gene therapy target. In this study, we constructed adenovirus expressing human p27 (ad-p27) and investigated its antitumor effects on human lung cancer cell lines. Upon transduction of several human lung cancer cells with ad-p27, a high level of p27 expression, with a decrease in cdk2 and an increase in cyclin E were observed. These changes resulted in G1/S arrest. Transduction of human lung cancer cell lines with ad-p27 showed in vitro growth inhibition and a marked suppression of colony formation upon soft agar clonogenic assay. Direct intratumoral injection of ad-p27 induced the growth suppression of established lung tumors in nude mice. From these observations, gene therapy using ad-p27 seems to offer a potential basis for the development of new cancer gene therapy modality and a useful tool to investigate the mechanisms of cell cycle control.
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KEYWORD
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Adenovirus-p27, Cell cycle, Lung cancer, Growth inhibition, Gene therapy,
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