title: Use of protein array technology to investigate receptor tyrosine kinases activated in hepatocellular carcinoma.
abstract: Receptor tyrosine kinases (RTKs) play a role in various processes, including cell growth, differentiation, apoptosis and carcinogenesis. RTKs are activated in various types of cancers, including breast, stomach, colon, pancreas and liver cancer and hepatocellular carcinoma (HCC). In the present study, protein array technology was used to analyze the expression status of various RTKs activated in HCC. The expression of activated RTKs was examined in the HCC cell lines, Alex, HuH7, Li-7, Hep3B, HLE and HLF; in the human normal hepatocyte cell line, hNHeps; and in human HCC and adjacent non-cancerous tissues. Of the 42 different phospho-RTKs, 15 (ErbB2, ErbB3, ErbB4, FGFR2α, FGFR3, insulin R, Mer, PDGFRβ, c-Ret, ROR2, Tie, TrkA, VEGFR3, EphA1 and EphA4) were activated in some of the cancer cell lines studied. Among these, only ErbB2 was activated in all the HCC cell lines examined. Also, in vitro experiments were performed in subcutaneous HCC-bearing athymic nude mice to determine the therapeutic effects of inhibiting ErbB2 activation using the ErbB2-targeting drug trastuzumab. The results revealed that trastuzumab markedly suppressed the growth of HCC. These data suggest that ErbB2 is activated in HCC and that trastuzumab may play a role in the treatment of this disease. In addition, the use of protein array technology is proposed as a tool for detecting the expression of activated RTKs and identifying an effective RTK-based therapy.
authors.affiliation: Departments of Gastroenterology and Neurology.
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.forename: Asahiro
authors.initials: A
authors.lastname: Morishita
authors.forename: Takako
authors.initials: T
authors.lastname: Nomura
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Joji
authors.initials: J
authors.lastname: Tani
authors.forename: Kiyohito
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authors.lastname: Kato
authors.forename: Hirohito
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authors.lastname: Yoneyama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Deguchi
authors.forename: Hirohito
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authors.lastname: Mori
authors.forename: Shima
authors.initials: S
authors.lastname: Mimura
authors.forename: Kei
authors.initials: K
authors.lastname: Nomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Himoto
authors.forename: Kazushi
authors.initials: K
authors.lastname: Deguchi
authors.forename: Keiichi
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authors.lastname: Okano
authors.forename: Kunihiko
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authors.lastname: Izuishi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yoshio
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authors.lastname: Kushida
authors.forename: Reiji
authors.initials: R
authors.lastname: Haba
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Iwama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki