Premium
Over‐expression of p27 kip1 induces growth arrest and apoptosis mediated by changes of pRb expression in lung cancer cell lines
Author(s) -
Naruse Ichiro,
Hoshino Hideki,
Dobashi Kunio,
Minato Koichi,
Saito Ryusei,
Mori Masatomo
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20001101)88:3<377::aid-ijc9>3.0.co;2-m
Subject(s) - apoptosis , cancer research , expression (computer science) , cell growth , lung cancer , cancer , biology , lung , cell cycle checkpoint , programmed cell death , medicine , microbiology and biotechnology , pathology , cell cycle , genetics , computer science , programming language
p27 kip1 is a cyclin‐dependent kinase inhibitor which controls the G 1 phase of the cell cycle in conjunction with pRb. p27 has been associated with cell‐cycle arrest and apoptosis. In this study, we transferred the full‐length human p27 cDNA using a replication‐deficient recombinant adenoviral vector (Ax‐p27) into lung cancer cell lines and evaluated the potential of this strategy for anti‐cancer gene therapy. After infection with Ax‐p27, the growth of H322, A549 and SQ‐5 cells, which express pRb, was almost completely suppressed, though no such effect was found in H69 and Lu‐135 cells, which do not express pRb. In addition, cell death from day 4 after infection with Ax‐p27 was observed only in H322, A549 and SQ‐5 cells but not in H69 and Lu‐135 cells. The cell cycle of H322 cells treated with Ax‐p27 became arrested at the G 1 phase from day 1 to day 3 despite continued over‐expression of p27. When we examined the changes in expression level of pRb and E2F‐1, which play important roles in cell‐cycle progression from G 1 to S phase, down‐regulation of pRb expression was detected in H322 cells 3 days after infection with Ax‐p27. These data suggest that (i) the growth‐inhibitory effect and induction of apoptosis by over‐expression of p27 require expression of pRb and (ii) adenovirus‐mediated p27 gene transfer may have promise as a novel strategy in cancer gene therapy. Int. J. Cancer 88:377–383, 2000. © 2000 Wiley‐Liss, Inc.