Use of protein array technology to investigate receptor tyrosine kinases activated in hepatocellular carcinoma.
Use of protein array technology to investigate receptor tyrosine kinases activated in hepatocellular carcinoma.
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DOI：
10.3892/etm.2011.215
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发表时间：
2011-05
影响因子：
2.7
通讯作者：
Shi Liu;J. Gong;A. Morishita;T. Nomura;Hisaaki Miyoshi;J. Tani;Kiyohito Kato;Hirohito Yoneyama;Akihiro Deguchi;H. Mori;Shima Mimura;Kei Nomura;T. Himoto;K. Deguchi;K. Okano;K. Izuishi;Yasuyuki Suzuki;Y. Kushida;R. Haba;H. Iwama;T. Masaki
中科院分区：
文献类型：
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作者：
Shi Liu;J. Gong;A. Morishita;T. Nomura;Hisaaki Miyoshi;J. Tani;Kiyohito Kato;Hirohito Yoneyama;Akihiro Deguchi;H. Mori;Shima Mimura;Kei Nomura;T. Himoto;K. Deguchi;K. Okano;K. Izuishi;Yasuyuki Suzuki;Y. Kushida;R. Haba;H. Iwama;T. Masaki
受体酪氨酸激酶（RTK）在细胞生长、分化、凋亡和癌变等过程中发挥重要作用。RTK在各种类型的癌症中被激活，包括乳腺癌、胃癌、结肠癌、胰腺癌和肝癌以及肝细胞癌（HCC）。本研究应用蛋白质芯片技术分析了肝癌组织中各种激活的RTK的表达状态。在HCC细胞系Alex、HuH 7、Li-7、Hep 3B、HLE和HLF中;在人正常肝细胞系hNHeps中;以及在人HCC和邻近非癌组织中检查活化的RTK的表达。在42种不同的磷酸-RTK中，15种（ErbB 2、ErbB 3、ErbB 4、FGFR 2 α、FGFR 3、胰岛素R、Mer、PDGFRβ、c-Ret、ROR 2、Tie、TrkA、VEGFR 3、EphA 1和EphA 4）在所研究的一些癌细胞系中被激活。其中，只有ErbB 2被激活，在所有的肝癌细胞系检查。此外，在皮下HCC荷瘤裸鼠中进行体外实验，以确定使用ErbB 2靶向药物曲妥珠单抗抑制ErbB 2活化的治疗效果。结果显示，曲妥珠单抗显著抑制HCC的生长。这些数据表明，ErbB 2在HCC中被激活，曲妥珠单抗可能在治疗这种疾病中发挥作用。此外，提出使用蛋白质阵列技术作为检测激活的RTK的表达和鉴定有效的基于RTK的疗法的工具。
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.