The Study Of Interaction Between Transcription Factors EGFR And STAT3 In Nuclear Of NPC Cells Regulated By LMP1

A transcription factor is a protein that binds DNA at specific sites where it can regulate transcription. Without transcription factors, the creation of new RNA from DNA cannot occur. Transcription factors can be activated or deactivated by other proteins.Belonging to the (receptor tyrosine kinases, RTKs) family, Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with a molecular mass of 170 kD. In recent years, high level of EGFR expression has been found in the nucleus of cells in various types of tumors such as skin cancer, breast cancer, cervical cancer, bladder cancer, ovarian cancer. As a new type of transcription factors, EGFR funtions either independently or together with other types of transcription factors as a transcriptional co-activator, acting on those target cells which are closely related to the cell cycle and cell proliferation, promoting the development of tumor. Transcription factor STAT3 (signal transducer and activation of transcription) is a key signaling molecule which plays a very important role in the functioning of a variety of cytokines and growth factors.By forming the homodimer or heterologous dimerization between tyrosine phosphorylated STAT3, STAT3 is activated and then translocates to the nucleus, activating the expression of numerous related downstream target genes. During the development of tumors, STAT3 promotes cell proliferation, immune evasion, angiogenesis, invasion and metastasis of tumor cells and inhibits cell apoptosis.EB virus (Epstein-Barr Virus, EBV) is a DNA oncogenic virus which is relevant to the malignant transformation of B cells, epithelial cells, T cells in the malignant transformation as well as the development of numerous types of tumor. This can largely be attributed to the protein encoded by the virus which influence gene expression in the host cell and relevant biological behavior. Being an EBV-encoded oncoprotein, the biological function of Latent membrane protein 1 (LMP1) involves in cell transformation, apoptosis, differentiation, cell cycle road, cancer invasion and metastasis.Preliminary studies found that LMP1 can regulate the expression level of EGFR and increase EGFR phosphorylation in NPC cells, thus promoting cell proliferation, also LMP1 could regulate nuclear translocation of EGFR by ligand EGF-independent way. At the same time, many of EGFR that can be directly combined with other transcription factors in the interaction of DNA can only play a biological role in promoting cell proliferation. Preliminary studies also found that LMP1 in nasopharyngeal carcinoma cells activate the JAK / STAT signaling pathway, through the promotion of JAK3 tyrosine 705 STAT3 phosphorylation and activation of STAT3 phosphorylation, which can result in nuclear translocation and nuclear accumulation of STAT3, and LMP1 regulation nuclear translocation of phosphorylated STAT3 was tyrosine phosphorylation-dependent 705. We speculate that LMP1 could regulate the interaction between EGFR and STAT3 by inducing their nuclear translocation. In order to observe whether EGFR and STAT3 co-locate in nucleus of NPC cells, the confocal laser scanning microscope is used. We found that EGFR and STAT3 co-locate in nucleus of CNE1-LMP1 cells which can express LMP1, while the negative control cells CNE1 are not. Furthermore, co-immunoprecipitation [(CO-IP)-western blot (WB)] indicate that LMP1 may promote EGFR and STAT3 binding as a complex in NPC cells. Then were done with the cytoplasm and nucleoprotein co-immunoprecipitation and western-blot analysis showed that combination of EGFR and STAT3 complex subcellular localization is the main nucleus. These results for the LMP1 EGFR and STAT3 transcription factors in the mechanism of the nucleus of nasopharyngeal carcinoma provide important experimental basis.In summary, this study found that EGFR and STAT3 transcription factor nuclear translocation and co-location in the presence of nasopharyngeal carcinoma which was LMP1 expression and LMP1 could induce EGFR/STAT3 complex combination with each other and the main part of its binding in the nucleus. This new discovery of protein interactions from the New Vision illustrates EGFR and STAT3 involved in cell cycle, a new mechanism for abnormal evolution of an important tumor EBV LMP1 protein function has been expanded, molecular targeted therapy for nasopharyngeal carcinoma develop a new target provides an experimental basis.