Bcl-2 in Cell-Cycle Regulation of Hematopoietic Cells by Transforming Growth Factor-β1

Publisher Website
Google Scholar
Abstract
We reported that several growth factors regulate the doubling lime of hematopoietic progenitor cells by modulating the time required to pass through the GI phase. As recent studies revealed the link between cell death and cell-cycle progression. we asked if cell death regulators such ss Bel-2 play a role in regulating the cell-cycle of hematopoietic cells by growth factors. Among growth factors. transforming growth factor-β1 (TCF-β1). a negative regulator of hematopoietis, was chosen. When a large number of cells was required for analysis, we used IL-3-dependent Ba/F3 cells instead of primary hematopoietic progenitor cells because the response of Ba/F3 cells to TGF-β1 was similar to that of primary hematopoietic progenitor cells. TGF-β1 decelerated the cell-cycling of hematopoietic cells by inducing a delay in G1 to S phase transition, an event associated with increase in the level of Bel-2 as well as p27. a cyclin/cyclin-dependent kinase inhibitor. In experiments using Ba/F3 cells with the potential to produce Bel-2 in an inducible manner. Bel-2 apparently functions upstream of p27. The effects of TGF-β1 on Bel-2 and p27 expression as well as cell growth were abrogated by c-kit ligand. These findings suggest that Bel-2 plays a crucial role in regulating the cell-cycle of hematopoietic progenitor cells.