Resistance to TGF-beta1 correlates with a reduction of TGF-beta type II receptor expression in Burkitt's lymphoma and Epstein-Barr virus-transformed B lymphoblastoid cell lines.
The pleiotropic cytokine TGF-beta1 is a member of a large family of related factors involved in controlling cell proliferation, differentiation and apoptosis. TGF-beta ligands interact with a complex of type I and type II transmembrane serine/threonine kinases and they transmit their signals to the nucleus via a family of Smad proteins. A panel of over 20 Burkitt's lymphoma (BL) cell lines has been compiled including those that are Epstein-Barr virus (EBV) negative, those that carry EBV with a restricted pattern of EBV latent gene expression (group I) and those that express the full range of latent EBV genes (group III), together with selected EBV-transformed lymphoblastoid cell lines (LCLs). Most of the EBV-negative and group I BL cell lines underwent apoptosis or a G(1) arrest in response to TGF-beta1 treatment. In contrast, group III cell lines and LCLs were completely refractory to these effects of TGF-beta1. All of the cell lines expressed the TGF-beta pathway Smads and the TGF-beta type I receptor. Lack of responsiveness to TGF-beta1 appears to correlate with a down-regulation of TGF-beta type II receptor expression. Studies of EBV-converted and stably transfected BL cell lines demonstrated that the EBV gene LMP-1 is neither necessary nor sufficient to block the TGF-beta1 response.
Inman
G J
GJ
Section of Virology and Cell Biology and the Ludwig Institute for Cancer Research, Imperial College of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Allday
M J
MJ
D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000235:genetics*; D002455:Cell Division; D002461:Cell Line, Transformed; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004351:Drug Resistance; D016193:G1 Phase; D015870:Gene Expression / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016296:Mutagenesis; D011061:Poly A; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014763:Viral Matrix Proteins / Q000235:genetics; D017735:Virus Latency
D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014763:Viral Matrix Proteins; D011061:Poly A; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II