Possible involvement of bcl-2 in regulation of cell-cycle progression of haemopoietic cells by transforming growth factor-beta1.
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.
Mahmud
N
N
The Second Department of Internal Medicine, Mie University School of Medicine, Edobashi, Tsu, Mie 514-8507, Japan.
Katayama
N
N
Nishii
K
K
Sugawara
T
T
Komada
Y
Y
Mitani
H
H
Araki
H
H
Ohishi
K
K
Watanabe
M
M
Masuya
M
M
Nishikawa
M
M
Minami
N
N
Ohashi
H
H
Shiku
H
H
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
D000911:Antibodies, Monoclonal; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta