EFFECT OF THE INTERACTION BETWEEN TRANSFORMING GROWTH-FACTOR-BETA ANDERYTHROPOIETIN ON THE PROLIFERATION OF NORMAL ERYTHROID PROGENITORS AND LEUKEMIC UT-7 CELLS - ACTION OF TRANSFORMING GROWTH-FACTOR-BETA ON THE ERYTHROPOIETIN RECEPTOR

The actions of transforming growth factor beta(TGF beta) and erythropo ietin (Epo) were studied using normal erythroid progenitors from fetal rat liver and spleen at 18, 19 and 20 days. rhTGF beta 1 inhibited th e growth of late BFUe colonies significantly at each age and in both o rgans in methylcellulose cultures containing 2 U/ml rhEpo. There was n o significant inhibition of CFUe proliferation, except for spleen CFUe at 18 days, suggesting different CFUe sensitivities to growth factors at a given fetal age, 18 days, in liver and spleen. The colorimetric MTT assay was used to examine the inhibition of the growth of human le ukemic UT-7 cells by TGF beta 1. TGF beta 1 inhibited the proliferatio n of UT-7 cells in cultures without Epo at 24 h and in cultures with E po at 24 and 72 h. The specific binding of [I-125]Epo to UT-7 surface was decreased by TGF beta 1 without any change in non-specific binding . TGF beta 1 also inhibited the expression of Epo-receptors on UT-7 ce lls, without changing receptor affinity. The inhibition of hematopoiet ic progenitor cell growth by TGF beta could involve altering the cell surface expression of growth factor receptors.