| Literature DB >> 15649431 |
Dai Shida1, Joji Kitayama, Hironori Yamaguchi, Hiroharu Yamashita, Ken Mori, Toshiaki Watanabe, Hirokazu Nagawa.
Abstract
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 1-phosphate (S1P), 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 S1P act upstream of HER2 in gastric cancer cells, and thus may act as potent stimulators of gastric cancer.Entities:
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Year: 2005 PMID： 15649431 DOI： 10.1016/j.bbrc.2004.12.088
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575