Effect of the interaction between transforming growth factor beta and erythropoietin 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 erythropoietin (Epo) were studied using normal erythroid progenitors from fetal rat liver and spleen at 18, 19 and 20 days. rhTGF beta 1 inhibited the growth of late BFUe colonies significantly at each age and in both organs in methylcellulose cultures containing 2 U/ml rhEpo. There was no 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 leukemic UT-7 cells by TGF beta 1. TGF beta 1 inhibited the proliferation of UT-7 cells in cultures without Epo at 24 h and in cultures with Epo at 24 and 72 h. The specific binding of [125I]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 cells, without changing receptor affinity. The inhibition of hematopoietic progenitor cell growth by TGF beta could involve altering the cell surface expression of growth factor receptors.
Leveque
E
E
Laboratoire de Biochimie, EP CNRS 89, UFR Sciences Exactes et Naturelles, Université de Reims, France.
Nagel
M D
MD
Haye
B
B
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D005865:Gestational Age; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000166:cytology / Q000196:embryology; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017467:Receptors, Erythropoietin / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000196:embryology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D009363:Neoplasm Proteins; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D004921:Erythropoietin