Recombinant adenovirus-mediated p14ARF overexpression sensitizes human breast cancer cells to cisplatin

Xiyun Deng, Min Kim, Didier Vandier, Yun jin Jung, Toshiki Rikiyama, Magda K. Sgagias, Merrill Goldsmith, Kenneth H. Cowan

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

p14ARF, the alternative product from the human INK4a/ARF locus, is one of the major targets for alterations in the development of human cancers. Overexpression of p14ARF results in cell cycle arrest and apoptosis. To examine the potential therapeutic role of re-expressing p14ARF gene product in human breast cancer, a recombinant adenovirus expressing the human p14ARF cDNA (Adp14ARF) was constructed and used to infect breast cancer cells. Five days after infection, Adp14ARF had considerable cytotoxicity on p53-wild-type MCF-7 cells. A time-course study showed that Adp14ARF infection of MCF-7 cells at 100 pfu/cell increased the number of cells in G0/G1 phase and decreased that in S and G2/M phases. The presence of apoptotic cells was confirmed using the TUNEL assay. Adp14ARF-mediated expression of p14ARF also resulted in a considerable increase in the amounts of p53 and its target proteins, p21WAF1 and MDM2. Furthermore, the combination treatment of MCF-7 cells with Adp14ARF and cisplatin resulted in a significantly greater cell death. Together, we conclude that p14ARF plays an important role in the induction of cell cycle arrest and apoptosis in breast cancer cells and recombinant adenovirus-mediated p14ARF expression greatly increases the sensitivity of these cells to cisplatin. These results demonstrate that the proper combination of Adp14ARF with conventional chemotherapeutic drug(s) could have potential benefits in treating breast cancer that carries wild-type p53 gene.

Original languageEnglish (US)
Pages (from-to)792-798
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume296
Issue number4
DOIs
StatePublished - 2002

Keywords

  • Apoptosis
  • Breast cancer
  • Cisplatin
  • Gene therapy
  • P14
  • Recombinant adenovirus

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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