Enhancement of prolactin (PRL)-stimulated mitogenesis of Nb2 rat lymphoma cell cultures by insulin-like growth factor I (IGF-I).
IGF-I stimulated the mitogenesis of Nb2 cells in the presence of suboptimal mitogenic concentrations of prolactin (PRL, 0.01 or 0.1 ng/ml). In the presence of 1 ng/ml or 10 ng/ml, concentrations of PRL that produced a maximal or near maximal mitogenic response in Nb2 cells, the addition of insulin-like growth factor-I (IGF-I) at 5 or 10 ng/ml did not further enhance mitogenesis. This effect was selective for IGF-I since IGF-II, epidermal growth factor (EGF), insulin, transforming growth factor-beta (TGF-beta) or platelet-derived growth factor (PDGF) did not stimulate mitogenesis in the presence or absence of PRL. That the ability of IGF-I to stimulate mitogenesis of these cells required PRL was suggested by the ability of PRL antiserum to block the IGF-I effect. Monoclonal antibody to IGF-I reduced the mitogenic response to one identical to PRL alone. In the presence of a suboptimal mitogenic concentration of PRL, IGF-I was an equally effective comitogen when added at 0 time or at 6 h after PRL stimulation, suggestive of an effect of IGF-I in late G1 phase of the cell cycle. Effects of IGF-I on ornithine decarboxylase, a G1 enzymatic marker, were compatible with this interpretation. In order to be assured that IGF-I exerted its action through a receptor-mediated process, we evaluated the presence of IGF-I receptors on Nb2 cells. Receptors were present which bound IGF-I greater than IGF-II much greater than insulin. The IC50 was 35 nM for IGF-I, 280 nM for IGF-II and 875 nM for insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Russell
D H
DH
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa 33612-4799.
Laird
H E
HE
D000818:Animals; D004357:Drug Synergism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008223:Lymphoma / Q000276:immunology; D008934:Mitogens; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology
D007457:Iodine Radioisotopes; D008934:Mitogens; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D009955:Ornithine Decarboxylase; D013936:Thymidine