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

研究成果: Article査読

31 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)706-711
ページ数6
ジャーナルCell Death and Differentiation
7
8
DOI
出版ステータスPublished - 2000

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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