Transforming growth factor beta inhibits growth of more differentiated myeloid leukemia cells and retinoblastoma protein phosphorylation at serine 795

Transforming growth factor beta (TGF-beta) has been shown to be a specific inhibitor of early human myeloid progenitors. me show here that TGF-beta 1 potentially inhibited not only the growth of primitive but also more mature myeloid leukemic cells. Surprisingly, those apparently more mature progeni tor cells, such as MV4-11 and Mo7e cells, are very sensitive to the action of TGF-beta. The addition of TGF-beta 1 to liquid cultures of these cells s ignificantly inhibited their proliferation, with as much as 72% inhibition of growth of MV4-11 cells. The suppressive effect by TGF-beta 1 was not rev ersed or prevented by granulocyte-macrophage colony-stimulating factor or i nterleukin 3 used to promote cell growth in TF-1a and MIV4-11 cells. TGF-be ta 1 completely abolished the clonal growth of MV4-11 cells in soft agar an d inhibited Mo7e, KG-1, K562, TF-1, and TF-la colony growth by 99%, 90%, 63 %, 53%, and 43%, respectively. The cells treated with TGF-beta 1 showed pro gressive accumulation in the G1 phase of cell cycle. Maximal G1 arrest (93% ) was observed in MV4-11 cells. Using anti-retinoblastoma protein (pRb) and anti-specific phosphorylated-pRb antibodies, me demonstrated that TGF-beta 1 greatly inhibited pRb phosphorylation at serine 795 in MV4-11 and Mo7e c ells. Taken together, our data suggest that the sensitivity of myeloid leuk emic progenitor cells to growth inhibition by TGF-beta may not be inversely correlated with their maturation stage, and the inhibition of the cells ap peared to be linked to the suppression of pRb phosphorylation at serine 795 . (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.