Induction of apoptosis in p16(INK4A) mutant cell lines by adenovirus-mediated overexpression of p16(INK4A) protein

M. Kim, Y. Katayose, L. Rojanala, S. Shah, M. Sgagias, L. Jang, Y. J. Jung, S. H. Lee, S. G. Hwang, K. H. Cowan

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Abstract

The tumor suppressor gene p16(INK4A) is a cyclin-dependent kinase inhibitor (CDKI) and an important cell cycle regulator. We have previously constructed a recombinant adenovirus which expresses p16 (Adp 16) and shown that infection in a variety of human tumor cell lines with this recombinant virus results in high levels of p16(INK4A) protein expression resulting in cell cycle arrest and loss of cyclin-cdk activity. Furthermore, adenoviral-mediated overexpression of wild-type p16(INK4A) is more toxic in cancer cells which express mutant forms of p16(INK4A) compared to cancer cell lines containing endogenous wild-type p16. TUNEL assay and DAPI staining following infection of MDA-MB 231 breast cancer cells with Adp16 indicate that p16(INK4A)-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating a decrease in cpp32 and cyclinB1 protein levels and induction of poly (ADP-ribose) polymerase (PARP) cleavage following infection of MDA-MB-231 cells with Adp16. These results suggest that gene therapy using Adp16 may be a promising treatment option for human cancers containing alterations in p16 expression.

Original languageEnglish (US)
Pages (from-to)706-711
Number of pages6
JournalCell Death and Differentiation
Volume7
Issue number8
DOIs
StatePublished - Jan 1 2000

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Keywords

  • Adenovirus
  • Apoptosis
  • Gene therapy
  • P16(INK4A)

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Kim, M., Katayose, Y., Rojanala, L., Shah, S., Sgagias, M., Jang, L., Jung, Y. J., Lee, S. H., Hwang, S. G., & Cowan, K. H. (2000). Induction of apoptosis in p16(INK4A) mutant cell lines by adenovirus-mediated overexpression of p16(INK4A) protein. Cell Death and Differentiation, 7(8), 706-711. https://doi.org/10.1038/sj.cdd.4400703