Flavell JR, Baumforth KRN, Wood VHJ, et al. Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus–encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells. Blood. 2008;111(1):292-301.

EBV infection or EBNA1 expression inhibits the TGF-beta–mediated activation of PTPRK expression and decreases total and phosphorylated Smad2 protein levels in HL cells. (A) TGF-beta stimulation of KM-H2 HL cells results in the robust up-regulation of PTPRK transcription. However, responsiveness to TGF-beta is reduced by the presence of EBV as demonstrated by a less marked increase in PTPRK transcription in EBV-positive HL cells compared with their EBV-negative counterparts. (B top panel) Immunoblotting shows a reduction in the levels of both total and phosphorylated Smad2 protein in EBV-positive HL cells. (B bottom panel) Semiquantitative RT-PCR demonstrates that SMAD2 transcription is unaffected by the presence of EBV in HL cells. (C) Immunoblotting demonstrates that expression of EBNA1 in EBV-negative KM-H2 cells is sufficient to reduce levels of total Smad2 protein. (D) Immunoblotting shows that expression of EBNA1 in 2 other EBV-negative HL cell lines, HDLM2 and L428, also results in the reduction of total Smad2 protein.