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

Int J Cancer. 2000 Nov 1;88(3):377-83.


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.

MeSH terms

  • Apoptosis*
  • Blotting, Western
  • Cell Cycle
  • Cell Cycle Proteins*
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p27
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Lung Neoplasms / pathology*
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / physiology*
  • Retinoblastoma Protein / analysis
  • Retinoblastoma Protein / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*


  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Retinoblastoma Protein
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27