Adenovirus expressing p27(Kip1) induces growth arrest of lung cancer cell lines and suppresses the growth of established lung cancer xenografts

p27(Kip1) (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...

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Bibliographic Details
Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2001-02, Vol.31 (2-3), p.149-155
Main Authors: Park, K H, Seol, J Y, Yoo, C G, Kim, Y W, Han, S K, Lee, E H, Kim, C M, Shim, Y S, Lee, C T
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - metabolism
Animals
Cell Cycle
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p27
DNA, Complementary - genetics
Genetic Therapy
Humans
Lung Neoplasms - metabolism
Lung Neoplasms - therapy
Mice
Mice, Nude
Microtubule-Associated Proteins - biosynthesis
Microtubule-Associated Proteins - genetics
Transplantation, Heterologous
Tumor Cells, Cultured
Tumor Suppressor Proteins
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Summary:p27(Kip1) (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.
ISSN:0169-5002
DOI:10.1016/S0169-5002(00)00195-1