Resistance to TGF-beta 1 correlates with a reduction of TGF-beta type II receptor expression in Burkitt's lymphoma and Epstein-Barr virus-transformedB lymphoblastoid cell lines

The pleiotropic cytokine TGF-beta 1 is a member of a large family of relate d factors involved in controlling cell proliferation, differentiation and a poptosis. TGF-beta ligands interact with a complex of type I and type II tr ansmembrane serine/threonine kinases and they transmit their signals to the nucleus via a family of Smad proteins, A panel of over 20 Burkitt's lympho ma (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 lympho blastoid cell lines (LCLs), Most of the EBV-negative and group I BL cell li nes underwent apoptosis or a G(1) arrest in response to TGF-beta 1 treatmen t. In contrast, group III cell lines and LCLs were completely refractory to these effects of TGF-beta 1. All of the cell lines expressed the TGF-beta pathway Smads and the TGF-beta type I receptor. Lack of responsiveness to T GF-beta 1 appears to correlate with a downregulation of TGF-beta type II re ceptor expression. Studies of EBV-converted and stably transfected BL cell lines demonstrated that the EBV gene LMP-1 is neither necessary nor suffici ent to block the TGF-beta 1 response.