c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-β signaling in diffuse-type gastric carcinoma

摘要: c-Ski, originally identified as a proto-oncogene product, is an important negative regulator of transforming growth factor (TGF)-β family signaling through interaction with Smad2, Smad3, and Smad4. High expression c-Ski has been found in some cancers, including gastric cancer. We previously showed that disruption TGF-β by dominant-negative type II receptor diffuse-type carcinoma model accelerated tumor induction angiogenesis decreased the anti-angiogenic thrombospondin (TSP)-1. Here, we examined function human OCUM-2MLN cells. Overexpression inhibited Interestingly, overexpression resulted extensive acceleration subcutaneous xenografts BALB/c nu/nu female mice (6 weeks age). Similar to tumors expressing receptor, histochemical studies revealed less fibrosis increased xenografted compared control tumors. Induction TSP-1 mRNA was attenuated in vitro, in vivo. These findings suggest promotes angiogenesis. (Cancer Sci 2009; 100: 1809–1816)