IGFBP-3 expression in hepatocellular carcinoma involves abnormalities in TGF-ß and/or Rb signaling pathways

Eiichiro Yumoto, Harushige Nakatsukasa, Tadashi Hanafusa, Yasuhiro Yumoto, Kazuhiro Nouso, Eiji Matsumoto, Toru Onishi, Yoshitaka Takuma, Hironori Tanaka, Tatsuya Fujikawa, Mayumi Suzuki, Masayuki Uemura, Yasushi Shiratori

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Insulin-like growth factor binding protein-3 (IGFBP-3) is a mediator of growth suppression signals and a putative tumor suppressor gene. The growth suppression mechanisms of IGFBP-3 have not been well clarified. We examined the expression of IGFBP-3 transcripts in human hepatocellular carcinoma (HCC) and the relationship between IGFBP-3 expression and the transforming growth factor-6 (TGF-ß) and/or retinoblastoma (Rb) signaling pathways. In situ hybridization revealed IGFBP-3 transcripts in cancer cells in 6 of 57 (10%) HCCs, including moderately and poorly differentiated HCCs with intrahepatic metastasis. In contrast, all lung metastatic nodules of 4 HCCs showed IGFBP-3 transcripts in cancer cells. The cDNA microarray showed that genes for the TGF-ß pathway and Rb were up-regulated in IGFBP-3-expressing HCCs. In 6 HCCs presenting IGFBP-3, immunohistochemical analyses showed abnormalities in the TGF-B and/or Rb pathways; the loss of phosphorylated-Smad2 was observed in 2, and overexpression of phosphorylated-Rb was observed in the remaining 4 HCCs. The present study suggests that IGFBP-3 mediates growth suppression signals via the TGF-B and/or Rb pathways in HCC.

    Original languageEnglish
    Pages (from-to)1223-1230
    Number of pages8
    JournalInternational journal of oncology
    Volume27
    Issue number5
    Publication statusPublished - Nov 2005

    Keywords

    • Hepatocellular carcinoma
    • In situ hybridization
    • Insulin-like growth factor binding protein-3
    • Retinoblastoma
    • Transforming growth factor-8

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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