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

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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 - 2000

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Induction of apoptosis in p16(INK4A) mutant cell lines by adenovirus-mediated overexpression of p16(INK4A) protein'. Together they form a unique fingerprint.

Cite this