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, Kenneth H Cowan

Research output: Contribution to journalArticle

28 Citations (Scopus)

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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Cyclin-Dependent Kinase Inhibitor p16
Adenoviridae
Apoptosis
Cell Line
Infection
Neoplasms
Cyclins
Poly(ADP-ribose) Polymerases
Cyclin-Dependent Kinases
Poisons
In Situ Nick-End Labeling
Cell Cycle Checkpoints
Tumor Cell Line
Tumor Suppressor Genes
Genetic Therapy
Cell Cycle
Staining and Labeling
Breast Neoplasms
Viruses

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Induction of apoptosis in p16(INK4A) mutant cell lines by adenovirus-mediated overexpression of p16(INK4A) protein. / Kim, M.; Katayose, Y.; Rojanala, L.; Shah, S.; Sgagias, M.; Jang, L.; Jung, Y. J.; Lee, S. H.; Hwang, S. G.; Cowan, Kenneth H.

In: Cell Death and Differentiation, Vol. 7, No. 8, 01.01.2000, p. 706-711.

Research output: Contribution to journalArticle

Kim, M, Katayose, Y, Rojanala, L, Shah, S, Sgagias, M, Jang, L, Jung, YJ, Lee, SH, Hwang, SG & Cowan, KH 2000, 'Induction of apoptosis in p16(INK4A) mutant cell lines by adenovirus-mediated overexpression of p16(INK4A) protein', Cell Death and Differentiation, vol. 7, no. 8, pp. 706-711. https://doi.org/10.1038/sj.cdd.4400703
Kim, M. ; Katayose, Y. ; Rojanala, L. ; Shah, S. ; Sgagias, M. ; Jang, L. ; Jung, Y. J. ; Lee, S. H. ; Hwang, S. G. ; Cowan, Kenneth H. / Induction of apoptosis in p16(INK4A) mutant cell lines by adenovirus-mediated overexpression of p16(INK4A) protein. In: Cell Death and Differentiation. 2000 ; Vol. 7, No. 8. pp. 706-711.
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