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Updated: Jun 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 to investigate receptor tyrosine kinases activated in gastric cancer
Jian Gong1, Asahiro Morishita, Kazutaka Kurokohchi
1Department of Gastroenterology and Neurology, Kagawa Medical University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Abstract:
Our study used protein array technology to analyze the expression status of various activated receptor tyrosine kinases (RTKs) in gastric carcinoma; then, we sought to discover an effective therapeutic receptor tyrosine kinase for this disease and investigated the anti-tumor mechanism of the therapeutic RTK. In addition to the expressions of activated RTKs in human gastric cancer and adjacent normal mucosa, the expression of activated RTKs in gastric cancer cell lines, MKN74, MKN45, MKN7 and MKN1, were also studied. The RTKs activated in gastric cancer tissue are EGFR, ErbB2, FGFR1, FGFR2alpha insulin R, and EphA4. Among the RTKs activated in gastric cancer tissues, EGFR and ErbB2 were also activated in all gastric cell lines examined in this study. A subsequent in vitro experiment using subcutaneous gastric cancer-bearing athymic nude mice demonstrated that the ErbB2-targeting drug trastuzumab markedly suppressed the growth of gastric cancer. Moreover, using an angiogenesis protein array, the expressions of Ang I, FGF-alpha, FGF-beta TGF-beta and IL-8 in MKN74 xenograft tumors were found to be significantly reduced by treatment with trastuzumab, indicating that trastuzumab may inhibit the expression of angiogenic molecules in MKN74 cells in vivo. These data suggest that ErbB2 is activated in gastric cancer, and the ErbB2-targeting drug trastuzumab may be related to the reduction of Ang 1, FGFalpha, FGFbeta, TGFalpha and IL-8.
Insights
This study identifies activated receptor tyrosine kinases (RTKs) in gastric cancer, finding ErbB2 is a potential therapeutic target. The ErbB2-targeting drug trastuzumab effectively suppressed tumor growth and reduced angiogenic factors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric carcinoma is a significant global health concern with complex molecular underpinnings.
- Receptor tyrosine kinases (RTKs) play crucial roles in cancer development and progression.
- Identifying actionable RTK targets is essential for developing effective gastric cancer therapies.
Purpose of the Study:
- To analyze the expression of activated RTKs in gastric carcinoma.
- To identify a potential therapeutic RTK target for gastric cancer.
- To investigate the anti-tumor mechanism of a targeted therapy.
Main Methods:
- Protein array technology was employed to assess activated RTK expression in tumor tissues and cell lines.
- In vitro and in vivo experiments utilized gastric cancer cell lines and xenograft models.
- Angiogenesis protein arrays were used to evaluate the impact of treatment on angiogenic factors.
Main Results:
- Activated RTKs including EGFR, ErbB2, FGFR1, FGFR2alpha, insulin R, and EphA4 were identified in gastric cancer.
- EGFR and ErbB2 were found to be activated in both tumor tissues and all examined gastric cancer cell lines.
- Treatment with trastuzumab, an ErbB2-targeting drug, significantly suppressed gastric cancer growth in vivo.
- Trastuzumab treatment led to a notable reduction in the expression of angiogenic molecules (Ang I, FGF-alpha, FGF-beta, TGF-beta, IL-8) in xenograft tumors.
Conclusions:
- ErbB2 is a key activated receptor tyrosine kinase in gastric cancer.
- Trastuzumab demonstrates significant anti-tumor efficacy against gastric cancer.
- The anti-tumor effect of trastuzumab may involve the inhibition of angiogenesis through the downregulation of specific angiogenic factors.
