Egr-1, a new downstream molecule of Epstein-Barr virus latent membrane protein 1

Kim, Joo Hyun; Kim, Won Seog; Kang, Jung Hun; Lim, Ho-Yeong; Ko, Young-Hyeh; Park, Chaehwa

doi:10.1016/j.febslet.2007.01.020

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Volume 581, Issue 4 , Pages 623-628, 20 February 2007

Egr-1, a new downstream molecule of Epstein-Barr virus latent membrane protein 1

Edited by Lukas Huber

Joo Hyun Kim
- Biomedical Research Institute, Samsung Medical Center, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
Won Seog Kim
- Biomedical Research Institute, Samsung Medical Center, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
- Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
- Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
- Corresponding authors. Address: Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea. Fax: +82 2 3410 0041 (W.S. Kim); +82 2 3410 6808 (C. Park).
Jung Hun Kang
- Department of Hematology-Oncology, Gyeongsang National University Hospital, Jinju, Republic of Korea
Ho-Yeong Lim
- Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
Young-Hyeh Ko
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
Chaehwa Park
- Biomedical Research Institute, Samsung Medical Center, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
- Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
- Corresponding authors. Address: Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea. Fax: +82 2 3410 0041 (W.S. Kim); +82 2 3410 6808 (C. Park).

Received 28 August 2006; received in revised form 5 December 2006; accepted 10 January 2007. published online 18 January 2007.

Abstract

To investigate the effect of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) on human cancer cells, we sought to identify and analyze potential target genes that were differentially expressed in the presence and absence of LMP1. Our cDNA microarray analysis revealed that expression of early growth response gene-1 (Egr-1) was increased by LMP1 expression in MCF7 and Jurkat cells. An NFκB inhibitor (SN50) antagonized LMP1-induced enhancement of Egr-1 expression, indicating that LMP1 induced Egr-1 via NFκB. Furthermore, three lines of evidence indicated that Egr-1 was required for LMP1-induced cancer cell survival. First, Egr-1 expression enhanced the survival of doxorubicin-treated MCF7 cells. Second, inhibition of Egr-1 expression by siRNA (siEgr-1) effectively suppressed LMP-1-induced survival of MCF7 cells. Third, Egr-1 knockdown decreased LMP1-induced expression of Bfl-1. Similar relationships among EBV infection, Egr-1 and drug resistance were also observed in tissues of peripheral T-cell lymphoma-unspecified (PTCL-u) patients.

Keywords: LMP1, Egr-1, Epstein-Barr virus, Survival