title: Use of protein array to investigate receptor tyrosine kinases activated in gastric cancer.
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.
authors: Department of Gastroenterology and Neurology, Kagawa Medical University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors: Jian
authors: J
authors: Gong
authors: Asahiro
authors: A
authors: Morishita
authors: Kazutaka
authors: K
authors: Kurokohchi
authors: Joji
authors: J
authors: Tani
authors: Kiyohito
authors: K
authors: Kato
authors: Hisaaki
authors: H
authors: Miyoshi
authors: Hideyuki
authors: H
authors: Inoue
authors: Mitsuyoshi
authors: M
authors: Kobayashi
authors: Shi
authors: S
authors: Liu
authors: Masayuki
authors: M
authors: Murota
authors: Akemi
authors: A
authors: Muramatsu
authors: Kunihiko
authors: K
authors: Izuishi
authors: Yasuyuki
authors: Y
authors: Suzuki
authors: Hirohito
authors: H
authors: Yoshida
authors: Naohito
authors: N
authors: Uchida
authors: Kazushi
authors: K
authors: Deguchi
authors: Hisakazu
authors: H
authors: Iwama
authors: Ichiro
authors: I
authors: Ishimaru
authors: Tsutomu
authors: T
authors: Masaki
mesh_terms: D000368:Aged; D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D040081:Protein Array Analysis / Q000379:methods*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D020794:Receptor Protein-Tyrosine Kinases