TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.
Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.
Farmer
John T
JT
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
Weigent
Douglas A
DA
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D000906:Antibodies; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D051899:Smad2 Protein; D051900:Smad3 Protein; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013006:Growth Hormone