In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3957-3957
Abstract:
To improve gastric cancer treatment, relevant molecular targets need to be identified. Receptor tyrosine kinases (RTKs) are multifunctional transmembrane proteins and important mediators of the signaling cascade, determining key roles in diverse biological processes like proliferation, growth, differentiation, and apoptosis of cancer cells. To determine if any of these RTKs are activated in gastric cancer, we performed phospho-receptor tyrosine kinase array with 25 gastric cancer cell lines using Human Phospho-RTK Antibody Proteome Profiler Array (R & D Systems) which includes 42 different tyrosine kinases. Relative levels of tyrosine phosphorylation of RTKs among these cell lines were determined as a ratio relative to four positive phosphorylated tyrosine kinase control's intensity in each membrane. We found that various growth factor receptor tyrosine kinases were differentially activated and 15 of 42 RTKs were highly activated with mean intensity & gt;5 among 25 gastric cancer cell lines. The highly activated RTKs were: EGFR (93.2), ErbB2 (33.0), HGFR (27.6), ErbB3 (26.2), IGF-IR (17.2), InsulinR (13.9), Mer (12.9), FGFR2α (11.4), Dtk (10.1), EphA7 (9.5), Tie-2 (8.9), MSPR (6.5), c-Ret (6.4), FGFR3 (5.4), and ErbB4 (5.1). These receptors basically belong to the EGF, HGF, FGF, Insulin, Tie, and Ephrin growth factor gene families_all of which are involved in cell proliferation, differentiation or signal transduction. We confirmed that increased RTKs phosphorylation observed by RTK array analysis was correlated with the expression level of each protein by immunoblotting. Additionally, we showed that Met gene amplification by quantitative real-time PCR is associated with Met activation in gastric cancer cell lines. In conclusion, these activated RTKs may work as potential therapeutic targets in gastric cancer and helpful to understand the molecular mechanisms underlying tumor development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3957.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-3957
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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