Egr-1, a new downstream molecule of Epstein-Barr virus latent membrane protein 1.
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 NFkappaB inhibitor (SN50) antagonized LMP1-induced enhancement of Egr-1 expression, indicating that LMP1 induced Egr-1 via NFkappaB. 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.
Kim
Joo Hyun
JH
Biomedical Research Institute, Samsung Medical Center, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea.
Kim
Won Seog
WS
Kang
Jung Hun
JH
Lim
Ho-Yeong
HY
Ko
Young-Hyeh
YH
Park
Chaehwa
C
D000998:Antiviral Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D024882:Drug Resistance, Viral / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006564:Herpesviridae / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
D000998:Antiviral Agents; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D051766:Early Growth Response Protein 1; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins