title: Loss of endogenous TGF-beta effect induces mouse hepatoma malignancy by correlation with cyclooxygenase-2 and VEGF.
abstract: The relation between transforming growth factor-beta (TGF-beta) and cyclooxygenase (COX) in hepatoma malignancy is not understood yet. To investigate regulation mechanism of endogenous TGF-beta on hepatoma, we established MH129F mouse hepatoma cell overexpressing the cytoplasmic domain of type II TGF-beta receptor (TRII). MH129F cell apoptosis was elevated almost 20% after 5 ng/ml TGF-beta1 treatment. However, soluble TRII-overexpressing cells (MH129F/TRIIs) did not show any change of growth pattern after TGF-beta1 treatment because MH129F/TRIIs cells blocked the growth inhibitory effect of TGF-beta1. In MH129F/TRIIs cells, expression of cycooxygenase-2 (COX-2) and bcl-2 was remarkably elevated, and then enhancement of COX-2 mediated induction of prostaglandin E(2) (PGE(2)) production up to 7-fold. Especially, vascular endothelial growth factor (VEGF) expression was regulated by COX-2 in MH129F/TRIIs cells, which were inhibited endogenous TGF-beta response. Implantation of 5x10(6) MH129F/TRIIs cells into nude mice showed the significantly enhanced tumor formation, and intensity of COX-2 expression was slightly higher in MH129F/TRIIs tumor section than control. Moreover, a strong antitumor response was observed in MH129F/TRIIs-bearing mice that were treated with a specific COX-2 inhibitor, celecoxib. Therefore, we suggest that COX-2 mediate the tumorigenicity of hepatoma cells blocking endogenous TGF-beta effect via VEGF regulation.
authors.affiliation: Division of Cardiovascular Disease, Department of Biomedical Sciences, National Institute of Health, #5 Nokbun-dong, Eunpyung-gu, 122-701, Seoul, South Korea
authors.forename: Kye Young
authors.initials: KY
authors.lastname: Kim
authors.forename: June Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Byeong Woo
authors.initials: BW
authors.lastname: Ahn
authors.forename: Pan Dong
authors.initials: PD
authors.lastname: Ryu
authors.forename: Myeong Jin
authors.initials: MJ
authors.lastname: Nam