TY - JOUR
T1 - IGFBP-3 expression in hepatocellular carcinoma involves abnormalities in TGF-ß and/or Rb signaling pathways
AU - Yumoto, Eiichiro
AU - Nakatsukasa, Harushige
AU - Hanafusa, Tadashi
AU - Yumoto, Yasuhiro
AU - Nouso, Kazuhiro
AU - Matsumoto, Eiji
AU - Onishi, Toru
AU - Takuma, Yoshitaka
AU - Tanaka, Hironori
AU - Fujikawa, Tatsuya
AU - Suzuki, Mayumi
AU - Uemura, Masayuki
AU - Shiratori, Yasushi
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - Hepatocellular carcinoma
KW - In situ hybridization
KW - Insulin-like growth factor binding protein-3
KW - Retinoblastoma
KW - Transforming growth factor-8
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UR - http://www.scopus.com/inward/citedby.url?scp=33644661433&partnerID=8YFLogxK
M3 - Article
C2 - 16211216
AN - SCOPUS:33644661433
SN - 1019-6439
VL - 27
SP - 1223
EP - 1230
JO - International journal of oncology
JF - International journal of oncology
IS - 5
ER -
