hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated with 5-fluorouracil

Shin Sasaki, Toshiaki Watanabe, Takashi Kobunai, Tsuyoshi Konishi, Hideki Nagase, Yoshikazu Sugimoto, Toshinori Oka, Hirokazu Nagawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Exogenous overexpression of hRFI, originally isolated in our laboratory, inhibits not only death receptor-mediated apoptosis but also the mitochondrial apoptosis induced by several chemotherapeutic agents including 5-fluorouracil (5-FU). Recently, it has become clear that hRFI targets and degradates caspase-8 and -10 in death receptor-mediated apoptosis by E3 ubiquitin activity in a ring finger domain homologous to that of X-chromosome-linked inhibitor of apoptosis protein (XIAP). However, the cellular mechanism of the inhibition of mitochondrial apoptosis by hRFI has not been fully elucidated. We prepared HCT116 overexpressing hRFI (HCT116/hRFI) cells and comprehensively analyzed the expression changes of 51 apoptosis-related genes with or without 5-FU treatment between HCT116/hRFI and mock cells using microfluidic low-density arrays. As a result, we identified four genes (Bcl-2, Bcl-XL, cIAP2, and CFLAR) whose expression was four or more times higher in HCT116/hRFI cells than in HCT116/LacZ cells, and found that Bcl-2 and the ratio of Bcl-2/Bax or Bcl-2/Bak were upregulated when HCT116/hRFI cells were treated with 5-FU. Furthermore, we also validated the up-regulation of Bcl-2 and Bcl-XL in HCT116/hRFI cells treated with 5-FU by Western blot analysis. Such evidence suggests that the modulation of Bcl-2 family proteins seen in 5-FU treatment plays an important role in the anti-apoptotic function of HCT116/hRFI cells.

Original languageEnglish
Pages (from-to)1293-1298
Number of pages6
JournalOncology reports
Volume15
Issue number5
DOIs
Publication statusPublished - 2006 May
Externally publishedYes

Keywords

  • 5-Fluorouracil
  • Bcl-2 family
  • HRFI
  • Low-density array
  • Mitochondrial apoptosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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