Possible involvement of <i>bcl‐2</i> in regulation of cell‐cycle progression of haemopoietic cells by transforming growth factor‐β1

Abstract

Transforming growth factor‐β1 (TGF‐β1) acts directly on haemopoietic progenitor cells to regulate their growth. To investigate a possible link between the action of TGF‐β1 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‐β1, 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‐β1‐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‐β1 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‐β1 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‐β1.