title: Expression of insulin-like growth factor-1 and insulin-like growth factor-1 receptors in EL4 lymphoma cells overexpressing growth hormone.
abstract: Almost all of the previous studies with growth hormone (GH) have been done with exogenously supplied GH and, therefore, involve actions of the hormone through its receptor. However, the actions of endogenous or lymphocyte GH are still unclear. In a previous study, we showed that overexpression of GH (GHo) in a lymphoid cell line resulted in protection of the cells to apoptosis mediated by nitric oxide (NO). In the present study, we show that the protection from apoptosis could be transferred to control cells with culture fluids obtained from GHo cells and blocked by antibodies to the insulin-like growth factor-1 (IGF-1) or antibodies to the IGF-1-receptor (IGF-1R). Northern and Western blot analysis detected significantly higher levels of IGF-1 in cells overexpressing GH. An increase in the expression of the IGF-1R in GHo cells was also detected by Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter luciferase constructs. Transfection of GHo cells with a dominant negative IGF-1R mutant construct blocked the generation of NO and activation of Akt seen in GHo cells compared to vector alone control EL4 cells. The results suggest that one of the consequences of the overexpression of GH, in cells lacking the GH receptor, is an increase in the expression of IGF-1 and the IGF-1R which mediate the protection of EL4 lymphoma cells from apoptosis.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham, 1918 University Blvd. MCLM894, Birmingham, AL 35294-0005, USA. Weigent@uab.edu
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Weigent
authors.forename: Robyn E
authors.initials: RE
authors.lastname: Arnold
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D009154:Mutation / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008741:Methyl Methanesulfonate; D017526:Receptor, IGF Type 1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt