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 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.
Park
K H
KH
Department of Internal Medicine, and Lung Institute of Medical Research Center, Seoul National University Hospital and College of Medicine, Gene Therapy Laboratory of Clinical Research Institute, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
Seol
J Y
JY
Yoo
C G
CG
Kim
Y W
YW
Han
S K
SK
Lee
E H
EH
Kim
C M
CM
Shim
Y S
YS
Lee
C T
CT
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018076:DNA, Complementary / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27