Interferon regulatory factor-1 gene abnormality and loss of growth inhibitory effect of interferon-α in human hepatoma cell lines

Shinichiro Tada, Hidetsugu Saito, Satoshi Tsunematsu, Hirotoshi Ebinuma, Kanji Wakabayashi, Tetsuya Masuda, Hiromasa Ishii

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28 Citations (Scopus)

Abstract

The effect of IFN-α on the growth of 5 hepatoma cell lines and a normal liver-derived cell line were examined. IFN dose-dependently inhibited the growth of cell lines except for HLE and Plc/PRF/5 in which the inhibition only occurred at a high concentration over 10,000 IU/ml. IFN-α-treatment induced the G1 arrest of these cells according to upregulation of p21(WAF- 1) expression, which is induced in PLC/PRF/5 and HLE only at a high IFN concentration. The receptor for IFN-α/β was well expressed in all the cell lines. DNA rearrangement of IRF-1 was detected in HLE and PLC/PRF/5 by Southern blotting, while IRF-2 gene was preserved. IFN-induced gene expressions were compared between HCC-T, HCC-M and PLC/PRF/5. RT-PCR demonstrated that the full-length IRF-1 and -2 mRNA was transcribed in all cell lines, but the mRNA amount of former gene in PLC/PRF/5 was less than that in HCC-T and HCC-M, about 1/10 by competitive RT-PCR. The sequence analysis of IRF-1 cDNA was performed and the full-length mRNA transcription was reconfirmed in PLC/PRF/5, but no significant point mutation was detected. These results suggest that IFN-α inhibits hepatoma growth by increasing p21(WAF-1) expression only when the IRF-1 gene is preserved normally.

Original languageEnglish
Pages (from-to)1207-1216
Number of pages10
JournalInternational journal of oncology
Volume13
Issue number6
Publication statusPublished - 1998 Dec 1

Keywords

  • Chronic hepatitis C
  • Hepatocellular carcinoma
  • Interferon
  • Interferon regulatory factor-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tada, S., Saito, H., Tsunematsu, S., Ebinuma, H., Wakabayashi, K., Masuda, T., & Ishii, H. (1998). Interferon regulatory factor-1 gene abnormality and loss of growth inhibitory effect of interferon-α in human hepatoma cell lines. International journal of oncology, 13(6), 1207-1216.