Effect of transforming growth factor-beta 1 on proliferation and induction of hemoglobin accumulation in K-562 cells.
The effects of transforming growth factor-beta 1 (TGF-beta 1) on proliferation and hemoglobinization in K-562 cells, a human multipotential hematopoietic cell line, were studied. We found that TGF-beta 1 could induce hemoglobin accumulation in K-562 cells. Various clones were selected on the basis of the inducibility of hemoglobinization by TGF-beta 1. One high response clone (no. 1) and one low response clone (no. 8) were studied in detail. Hemoglobin accumulation peaked on day 5 of culture in the presence of TGF-beta 1 (0.5 ng/mL, 20 pmol/L), when 90% of clone 1 cells, 55% of parent line cells, and less than 10% of clone 8 cells contained hemoglobin. There was a concomitant reduction in proliferation of 60% for clone 1, 40% for the parent line, and 30% for the clone 8 on day 5 of culture. Quantitative analysis showed that the hemoglobin contents in clone 1 after 5-day induction by TGF-beta 1 and hemin were 1.0 pg/cell and 2.9 pg/cell, respectively. The hemoglobin induced by TGF-beta 1 showed the same electrophoretic characteristics as the hemoglobin induced by hemin. The expression of epsilon-globin mRNA was minimally detectable in control cells and was induced in both TGF-beta 1 and hemin treated cells. Other cytokines with potential effects on K-562 cell proliferation and differentiation were also studied. Interleukin-1, interleukin-3, interferon alpha, interferon gamma, and inhibin, tested as single agents, showed minimal effects on proliferation. None of these agents could induce hemoglobinization or inhibit the hemoglobinization induced by TGF-beta 1.
Chen
L L
LL
Laboratory of Receptor Biology, Sloan-Kettering Institute, New York, NY.
Dean
A
A
Jenkinson
T
T
Mendelsohn
J
J
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D005914:Globins / Q000235:genetics; D006427:Hemin / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006454:Hemoglobins; D012333:RNA, Messenger; D006427:Hemin; D015291:Transforming Growth Factors; D005914:Globins