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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Over-expression of p27kip1 induces growth arrest and apoptosis mediated by changes of pRb expression in lung cancer cell lines.

p27kip1 is a cyclin-dependent kinase inhibitor which controls the G1 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 G1 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 G1 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.[1]

References

  1. Over-expression of p27kip1 induces growth arrest and apoptosis mediated by changes of pRb expression in lung cancer cell lines. Naruse, I., Hoshino, H., Dobashi, K., Minato, K., Saito, R., Mori, M. Int. J. Cancer (2000) [Pubmed]
 
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