title: Possible involvement of bcl-2 in regulation of cell-cycle progression of haemopoietic cells by transforming growth factor-beta1.
abstract: Transforming growth factor-beta1 (TGF-beta1) acts directly on haemopoietic progenitor cells to regulate their growth. To investigate a possible link between the action of TGF-beta1 and cell death regulators such as bcl-2, we utilized Ba/F3 cells, the interleukin-3 (IL-3)-dependent growth of which could be modulated by TGF-beta1, as well as haemopoietic progenitor cells. We demonstrate here that up-regulation of bcl-2 protein (Bcl-2) as well as that of an inhibitor of cyclin/cyclin-dependent kinase complex, p27, was associated with TGF-beta1-induced deceleration of the cell-cycling of haemopoietic progenitor cells and Ba/F3 cells. The data from cell-cycle analysis of Ba/F3 cells showed that TGF-beta1 retarded the G1 to S phase transition. Analysis of cells with the potential to express Bcl-2 in an inducible manner indicated that up-regulation of Bcl-2 was sufficient for not only an increase in the level of p27 but also to inhibit the cell growth. Using c-kit-overexpressing cells, we observed that the potential of TGF-beta1 to up-regulate the expression of Bcl-2 and p27 could be counteracted by the c-kit ligand, stem cell factor. These results demonstrate that Bcl-2 exerts an essential function in the regulation of G1 to S phase transition of haemopoietic cells by TGF-beta1.
authors.affiliation: The Second Department of Internal Medicine, Mie University School of Medicine, Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mahmud
authors.forename: N
authors.initials: N
authors.lastname: Katayama
authors.forename: K
authors.initials: K
authors.lastname: Nishii
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: Y
authors.initials: Y
authors.lastname: Komada
authors.forename: H
authors.initials: H
authors.lastname: Mitani
authors.forename: H
authors.initials: H
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Ohishi
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Masuya
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: N
authors.initials: N
authors.lastname: Minami
authors.forename: H
authors.initials: H
authors.lastname: Ohashi
authors.forename: H
authors.initials: H
authors.lastname: Shiku
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000502:physiology; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta