Epstein-Barr Virus encoded LMP1 regulates cyclin D1 promoter activity by nuclear EGFR and STAT3 in CNE1 cells.
The principal Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1) is strongly associated with nasopharyngeal carcinoma (NPC), a prevalent cancer in China. The epidermal growth factor receptor (EGFR) is important in carcinogenesis, as it is a ubiquitously expressed receptor tyrosine kinase. Signal transducer and activator of transcription 3 (STAT3) is a master transcriptional regulator in proliferation and apoptosis. Our previous study demonstrated that the nuclear EGFR could bind to the cyclin D1 promoter directly in the presence of LMP1, and the correlation between EGFR and STAT3 in NPC remains to be further explored. Here, we have shown that the interaction of EGFR and STAT3 increased in the nucleus in the presence of LMP1. LMP1 promoted both EGFR and STAT3 binding to the promoter region of cyclin D1, in turn, enhancing the promoter activity of cyclin D1. Furthermore, we demonstrated that both transcriptional activity and mRNA levels of cyclin D1 were decreased by small molecule interference of EGFR and STAT3 activity. These findings may provide a novel linkage between the EGFR and STAT3 signaling pathways and the activation of cyclin D1 by LMP1 in the carcinogenesis of NPC.
Yang
Y
Xu
Ying
Y
Shi
Qi
Q
Yuan
Xuli
X
Liu
Bin
B
Yan
Ling
L
Chen
Cancer Research Institute, Central South University, Changsha, Hunan 410078, China. taoyong@csu.edu.cn.
Yongguang
Y
Tao
Ya
Y
Cao
D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism
C530104:CCND1 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014763:Viral Matrix Proteins; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors