Gene expression analysis of TGF-beta signaling-disrupting gastric cancer cell line 2MLN

Diffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)- and thick stromal fibrosis. However, detailed investigations on the roles of TGF- signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF- type II receptor expressing cells (2MLN-dnTRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTRII tumors. This results suggested disruption of TGF- signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth.

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Komuro A, Yashiro M, Iwata C, Morishita Y, Johansson E, Matsumoto Y, Watanabe A, Aburatani H, Miyoshi H, Kiyono K, Shirai YT, Suzuki HI, Hirakawa K, Kano MR, Miyazono K