Colorectal Cancer
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2005; 11(36): 5638-5643
Published online Sep 28, 2005. doi: 10.3748/wjg.v11.i36.5638
Lysophosphatidic acid transactivates both c-Met and epidermal growth factor receptor, and induces cyclooxygenase-2 expression in human colon cancer LoVo cells
Dai Shida, Joji Kitayama, Hironori Yamaguchi, Hiroharu Yamashita, Ken Mori, Toshiaki Watanabe, Hirokazu Nagawa
Dai Shida, Joji Kitayama, Hironori Yamaguchi, Hiroharu Yamashita, Ken Mori, Toshiaki Watanabe, Hirokazu Nagawa, Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
Author contributions: All authors contributed equally to the work.
Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a grant from the Ministry of Health, Labour and Welfare of Japan
Correspondence to: Dr. Dai Shida, Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. dshida-tky@umin.ac.jp
Telephone: +81-3-5800-8653 Fax: +81-3-3811-6822
Received: December 10, 2004
Revised: March 3, 2005
Accepted: March 9, 2005
Published online: September 28, 2005
Abstract

AIM: To examine whether lysophosphatidic acid (LPA) induces phosphorylation of c-Met and epidermal growth factor receptor (EGFR), both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 (COX-2) expression in human colon cancer cells.

METHODS: Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis, followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis.

RESULTS: Immunoprecipitation analysis revealed that 10 µmol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 µmol/L LPA induced COX-2 expression in a dose-dependent manner.

CONCLUSION: Our results suggest that LPA acts upstream of various receptor tyrosine kinases (RTKs) and COX-2, and thus may act as a potent stimulator of colorectal cancer.

Keywords: Lysophosphatidic acid, c-Met, EGFR, Transactivation, Cyclooxygenase-2, Colon cancer