Expression of insulin-like growth factors IGF-I and IGF-II, and their receptors during the growth and megakaryocytic differentiation of K562 cells.
Insulin-like growth factors (IGFs) I and II are critical regulators of cell proliferation and differentiation and most of the growth promoting properties of both ligands are mediated by IGF-I receptor (IGF-IR). In the present study we have investigated the role of IGFs in K562 cell line during normal growth and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced megakaryocytic differentiation. Abundant expression of IGF-I, IGF-II and IGF-IR was demonstrated in resting cells and exogenous IGF-I and IGF-II increased 3H-thymidine incorporation in a dose dependent manner. In contrast, we found that basal growth of the cells was inhibited by using anti-IGF-IR mAb. Furthermore, also IGF-I and IGF-II induced DNA synthesis was significantly suppressed by anti-IGF-IR mAb. During megakaryocytic differentiation, expression of IGF-IR increased during first 12h, but after that the expression started to decrease together with IGF-I. Taken together, our data suggest that autocrine production of IGF-I and IGF-II may via IGF-IR play a significant role in the growth and megakaryocytic differentiation of K562 cells.
Transplantation Laboratory, Haartman Institute, Helsinki University Central Hospital, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, Helsinki, Finland. aapo.aro@helsinki.fi
Aapo L A
AL
Aro
Johanna
J
Savikko
Ville
V
Pulkkinen
Eva
E
von Willebrand
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019898:Autocrine Communication; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D020014:K562 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D021122:Protein Subunits; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D021122:Protein Subunits; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D013755:Tetradecanoylphorbol Acetate