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Updated: May 18, 2026
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Use of protein array technology to investigate receptor tyrosine kinases activated in hepatocellular carcinoma
Shi Liu1, Jian Gong, Asahiro Morishita
1Departments of Gastroenterology and Neurology.
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.
Insights
Receptor tyrosine kinases (RTKs) are activated in hepatocellular carcinoma (HCC). The study found ErbB2 is activated in all HCC cell lines, and trastuzumab effectively suppressed tumor growth, suggesting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Receptor tyrosine kinases (RTKs) are crucial in cell growth, differentiation, apoptosis, and carcinogenesis.
- Aberrant RTK activation is implicated in various cancers, including hepatocellular carcinoma (HCC).
Purpose of the Study:
- To investigate the expression status of activated RTKs in HCC using protein array technology.
- To evaluate the therapeutic potential of targeting ErbB2 in HCC.
Main Methods:
- Protein array technology was employed to analyze activated RTK expression in HCC cell lines and patient tissues.
- In vitro experiments in HCC-bearing mice assessed the efficacy of the ErbB2-targeting drug trastuzumab.
Main Results:
- Out of 42 phospho-RTKs analyzed, 15 were activated in HCC cell lines, with ErbB2 being activated in all examined lines.
- Trastuzumab treatment significantly inhibited the growth of HCC tumors in vivo.
- Protein array technology proved effective in identifying activated RTKs and potential therapeutic targets.
Conclusions:
- ErbB2 is a key activated RTK in HCC.
- Trastuzumab demonstrates therapeutic promise for HCC treatment.
- Protein array technology is a valuable tool for RTK-based cancer therapy development.
