Protein expression profiles of necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine in mouse cancer cells

Akira Sato, Akito Satake, Akiko Hiramoto, Yusuke Wataya, Hye Sook Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We have investigated the molecular mechanisms regulating the necrosis and apoptosis that occur on treatment of mouse mammary tumor FM3A cells with 5-fluoro-2′-deoxyuridine (FUdR), a potent anticancer agent, using the original clone F28-7 and its variant F28-7-A cells. Previously, we reported an interesting observation that FUdR induces a necrotic morphology in F28-7 but an apoptotic morphology in F28-7-A cells. We have now analyzed the protein expression profiles of these FUdR-induced necrosis and apoptosis. Thus, proteome analysis of these clones by two-dimensional gel electrophoresis and mass spectrometry showed that the cytoplasmic intermediate filament protein, cytokeratin-19, is expressed at a significantly higher level in F28-7 than in F28-7-A cells. This strong expression was detected both in untreated and FUdR-treated stages of F28-7 cells. We interpreted this phenomenon as suggesting that cytokeratin-19 possesses a function in leading the cell to apoptosis. We performed a knockdown of cytokeratin-19 expression in F28-7 cells by use of the small interfering RNA technique. Indeed, a lowering of the cytokeratin-19 expression down to the level in F28-7-A occurred, and the FUdR-induced death morphology of this knockdown F28-7 was apoptosis, instead of the necrosis usually observable in the FUdR-treated F28-7. It is known that the cytoskeletal protein cytokeratin-19 undergoes caspase-mediated degradation during apoptosis. Our present finding provides an interesting possibility that cytokeratin-19 may have a key role in regulating cell-death morphology.

Original languageEnglish
Pages (from-to)2329-2338
Number of pages10
JournalJournal of Proteome Research
Volume9
Issue number5
DOIs
Publication statusPublished - May 7 2010

Keywords

  • 5-fluoro-2′-deoxyuridine (FUdR)
  • Apoptosis
  • Cell death
  • Cytokeratin-19
  • Intermediate filament
  • Lamin B1
  • Necrosis
  • Proteome analysis
  • SiRNA

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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