Dominant expression of survival signals of endoplasmic reticulum stress response in Hodgkin lymphoma

Kung-Chao Chang, Paul C H Chen, Ya-Ping Chen, Yao Chang, Ih Jen Su

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Abstract

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.

Original languageEnglish
Pages (from-to)275-281
Number of pages7
JournalCancer Science
Volume102
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

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Endoplasmic Reticulum Stress
Hodgkin Disease
Human Herpesvirus 4
MAP Kinase Kinase Kinase 5
Activating Transcription Factor 6
Endoplasmic Reticulum
Membrane Proteins
Transfection
Viral Proteins
Cell Survival
Carrier Proteins
Apoptosis
Cell Line
Epstein-Barr virus EBV-associated membrane antigen
glucose-regulated proteins
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

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title = "Dominant expression of survival signals of endoplasmic reticulum stress response in Hodgkin lymphoma",
abstract = "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.",
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Dominant expression of survival signals of endoplasmic reticulum stress response in Hodgkin lymphoma. / Chang, Kung-Chao; Chen, Paul C H; Chen, Ya-Ping; Chang, Yao; Su, Ih Jen.

In: Cancer Science, Vol. 102, No. 1, 01.01.2011, p. 275-281.

Research output: Contribution to journalArticle

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