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

  • Authors:
    • Shin Sasaki
    • Toshiaki Watanabe
    • Takashi Kobunai
    • Tsuyoshi Konishi
    • Hideki Nagase
    • Yoshikazu Sugimoto
    • Toshinori Oka
    • Hirokazu Nagawa
  • View Affiliations

  • Published online on: May 1, 2006     https://doi.org/10.3892/or.15.5.1293
  • Pages: 1293-1298
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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.

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May 2006
Volume 15 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Sasaki S, Watanabe T, Kobunai T, Konishi T, Nagase H, Sugimoto Y, Oka T and Nagawa H: hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated with 5-fluorouracil. Oncol Rep 15: 1293-1298, 2006
APA
Sasaki, S., Watanabe, T., Kobunai, T., Konishi, T., Nagase, H., Sugimoto, Y. ... Nagawa, H. (2006). hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated with 5-fluorouracil. Oncology Reports, 15, 1293-1298. https://doi.org/10.3892/or.15.5.1293
MLA
Sasaki, S., Watanabe, T., Kobunai, T., Konishi, T., Nagase, H., Sugimoto, Y., Oka, T., Nagawa, H."hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated with 5-fluorouracil". Oncology Reports 15.5 (2006): 1293-1298.
Chicago
Sasaki, S., Watanabe, T., Kobunai, T., Konishi, T., Nagase, H., Sugimoto, Y., Oka, T., Nagawa, H."hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated with 5-fluorouracil". Oncology Reports 15, no. 5 (2006): 1293-1298. https://doi.org/10.3892/or.15.5.1293