Use of protein array technology to investigate receptor tyrosine kinases activated in hepatocellular carcinoma

Liu,Shi; Gong,Jian; Morishita,Asahiro; Nomura,Takako; Miyoshi,Hisaaki; Tani,Joji; Kato,Kiyohito; Yoneyama,Hirohito; Deguchi,Akihiro; Mori,Hirohito; Mimura,Shima; Nomura,Kei; Himoto,Takashi; Deguchi,Kazushi; Okano,Keiichi; Izuishi,Kunihiko; Suzuki,Yasuyuki; Kushida,Yoshio; Haba,Reiji; Iwama,Hisakazu; Masaki,Tsutomu

doi:10.3892/etm.2011.215

Use of protein array technology to investigate receptor tyrosine kinases activated in hepatocellular carcinoma

Authors:
- Shi Liu
- Jian Gong
- Asahiro Morishita
- Takako Nomura
- Hisaaki Miyoshi
- Joji Tani
- Kiyohito Kato
- Hirohito Yoneyama
- Akihiro Deguchi
- Hirohito Mori
- Shima Mimura
- Kei Nomura
- Takashi Himoto
- Kazushi Deguchi
- Keiichi Okano
- Kunihiko Izuishi
- Yasuyuki Suzuki
- Yoshio Kushida
- Reiji Haba
- Hisakazu Iwama
- Tsutomu Masaki
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Affiliations: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa 761-0793, Japan, Department of Gastroenterological Surgery, Kagawa University School of Medicine, Kagawa 761-0793, Japan, Department of Diagnostic Pathology, Kagawa University School of Medicine, Kagawa 761-0793, Japan, Information Technology Center, Kagawa University School of Medicine, Kagawa 761-0793, Japan
Published online on: February 8, 2011 https://doi.org/10.3892/etm.2011.215
Pages: 399-403

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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.

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