Lysophospholipids transactivate HER2/neu (erbB-2) in human gastric cancer cells

被引：25

作者：

Shida, D ^{[1
]}

Kitayama, J ^{[1
]}

Yamaguchi, H ^{[1
]}

Yamashita, H ^{[1
]}

Mori, K ^{[1
]}

Watanabe, T ^{[1
]}

Nagawa, H ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Surg Oncol, Tokyo 1138655, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 327卷 / 03期

关键词：

HER2/neu; lysophosphatidic acid; sphingosine; 1-phosphate; lysophospholipid; transactivation; receptor tyrosine kinase; gastric cancer;

D O I：

10.1016/j.bbrc.2004.12.088

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The ligand-less receptor HER2/neu (erbB-2) has been proposed as a prognostic marker of gastric cancer that correlates with poor clinical outcome, indicating that HER2 signals play an important role in gastric cancer progression. This study demonstrated that two Major natural lysophospholipids, lysophosphatidic acid (LPA) and sphingosine I-phosphate (SIP), induce rapid and transient phosphorylation of HER2 in two human gastric cancer cell lines, MKN28 and MKN74 cells. We also revealed that tyrosine phosphorylation of HER2 induced by both lysophospholipids was significantly attenuated by two inhibitors, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AG1478, and a broad-spectrum matrix metalloproteinase inhibitor, GM6001. This suggests that the pathway of HER2 transactivation induced by these lysophospholipids is dependent on the proteolytically released EGFR ligands. Our results indicate that LPA and SIP act upstream of HER2 in gastric cancer cells, and thus may act as potent stimulators of gastric cancer. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：907 / 914

页数：8

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