
Dominant expression of survival signals of endoplasmic reticulum stress response in Hodgkin lymphoma
Author(s) -
Chang KungChao,
Chen Paul C.H.,
Chen YaPing,
Chang Yao,
Su IhJen
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01765.x
Subject(s) - xbp1 , unfolded protein response , chop , atf6 , endoplasmic reticulum , transfection , biology , cancer research , programmed cell death , apoptosis , signal transduction , activating transcription factor , microbiology and biotechnology , lymphoma , cell culture , immunology , rna splicing , gene , genetics , rna
The accumulation of viral proteins in endoplasmic reticulum (ER) may cause ER stress responses and lead to either apoptosis or survival depending on the driving signals. The strong expression of latent membrane protein‐1 (LMP1) in Epstein–Barr virus (EBV)‐positive Hodgkin lymphoma (HL) cells raises the question whether LMP1‐induced ER stress response is associated with the characteristic tumor biology in HL. In this study, we investigated the expression of ER stress signals (glucose‐regulated protein 78 [GRP78], X‐box binding protein 1 [XBP1], activating transcription factor 6 [ATF6], CCAAT enhance‐binding protein homologous protein [CHOP] and phospho‐apoptosis signal‐regulating kinase 1 [pASK1]) on 156 cases of HL. Furthermore, LMP1 transfection on EBV‐negative HL cell lines was used to explore the regulation of ER stress signals by EBV‐LMP1. Interestingly, we demonstrated that the survival signals of ER stress response (GRP78, 62%; XBP1u [unspliced], 55%; XBP1s [spliced], 38%; ATF6, 91%) were dominantly expressed over the ER death signals (CHOP, 10%; pASK1, 7%) in all histological subtypes of HL with a similar level in both EBV‐positive and EBV‐negative cases. However, expression of ER signals did not bear prognostic significance. In vitro, LMP1 transfection increased the expression of GRP78 and XBP1, but attenuated the expression of death signals, CHOP and pASK1. These data indicate that EBV‐LMP1 may play a role in shifting EBV‐infected cells towards the survival pathway in the presence of ER stress in EBV‐positive HL cases. ( Cancer Sci 2011; 102: 275–281)