title: TGF-beta1-induced cell growth arrest and partial differentiation is related to the suppression of Id1 in human hepatoma cells.
abstract: Transforming growth factor beta 1 (TGF-beta1) is a proposed regulator of Ids (inhibitors of DNA binding/differentiation) gene expression in epithelial cells. We previously reported that Id proteins are variously expressed in human hepatocellular carcinomas (HCC). However, the mechanism of regulation of Ids in HCC remains obscure. Here, we examined the relationship between Id1 and TGF-beta1 in four HCC cell lines, and studied the changes in cell proliferation, cell cycle and differentiation. The four HCC cell lines expressed Id1, TGF-beta1 and their receptors at various levels. TGF-beta1 strongly inhibited the growth of HuH7 cells, while the growth inhibition was moderate in PLC/PRF/5, and was not observed in HLE and HLF cell lines. TGF-beta1-induced growth inhibition in HuH7 cells was associated with cell accumulation in the G1 phase and partial induction of differentiation (with reduction of AFP and AFP-L3). Induction by TGF-beta1 dose-dependently suppressed Id1 expression in HuH7 cells; 1 ng/ml TGF-beta1 inhibited Id1 by 84.0 and 78.6% that of the untreated control at transcriptional and protein levels, respectively. HLE and HLF cells, which did not exhibit a TGF-beta1 growth inhibitory effect, lacked TGF-beta receptors and Id1 expression was not altered. In PLC/PRF/5 cells, Id1 augmentation was not observed in response to TGF-beta1, indicating that TGF-beta1-induced growth inhibition was not related to Id1 in this cell line. Our results suggest that, in some HCC cells, the pathway of suppression of Id1 by TGF-beta1 may be important in TGF-beta1-induced growth inhibition and partial differentiation.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, E2, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Bazarragchaa
authors.initials: B
authors.lastname: Damdinsuren
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Motoi
authors.initials: M
authors.lastname: Kondo
authors.forename: Javzandulam
authors.initials: J
authors.lastname: Natsag
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hanada
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kato
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D016212:Transforming Growth Factor beta