Down-regualtion Of Human DAB2IP Gene Expression Mediated By EZH2 In Endometrial Cancer Cells HEC-1-B And RL-952

Background and ObjectiveEndometrial cancer is the common maligant neoplasm in female reproductive system. The activation of oncogenes, the inactivation etc may involve the process of endometial cancer. Perturbations of the transcriptional memory of a cell may lead to developmental defects and cancer. As we known, two groups of proteins have long been found to be involved in the maintenace of heritable transcription patterns: The Polycomb Group (PcG) of proteins and their counterparts the Trithorax Group (TrxG) of proteins. PcG proteins have been implicated in fundamental cellular processes such as cell fate and cell division, as well as in neoplastic transformation .EZH2(enhancer of zeste homolog 2), a member of PcG family, plays a crucial role in the regulation of embryonic development and has been associated with the regulation of the cell cycle. Recently, several studies have shown that EZH2 is highly expressed in aggressive tumours, including human breast cancer, prostate cancer, lymphomas and so on. As a transcription inhibitor, EZH2 can supress a lot of genes, especially the metastasis-suppressing genes. So EZH2 can promote invasion and metastases of tumor cells.hDAB2IP (human DAB2 interactive protein) is a tumor suppressor gene belonging to Ras GTPase-activating family. Furthermore, DAB2IP can activate ASK1-JNK apoptotic signaling, and lead to tumor cells apoptosis. DAB2IP is down-regulated in various human cancers, such as prostate cancer, lung cancer, breast cancer and so on. It was manifested that the DNA hypermethylation and/or histone modification of DAB2IP promoter resulted in the down-regualtion of DAB2IP, however, its role and mechanism in cancer is largely unknown. So far few studies have been found on the expression levels of EZH2 and DAB2IP as well as the relationship of them in endometrial cancer cells. In our study, we focus on the down-reguation of DAB2IP gene expression mediated by EZH2 in endometrial cancer cells HEC-1-B and RL-952.Materials and MethodsFirstly, we tested the expression levels of EZH2 and DAB2IP in endometrial cancer cells HEC-1-B and RL-952 by using cell immunocytochemistry, immunological imprinting and real time PCR. Nextly, koncking EZH2 by siRNA, we observed the expression levels of EZH2 and DAB2IP by immunological imprinting at 24h, 48h, 72h, 96h, respectively.Results(1) After the test of cell Immunocytochemistry, immunological imprinting and real time PCR, we found that EZH2 has a higher level expression in the endomentral cancer cells HEC-1-B and RL-952, on the contrary, DAB2IP was relatively lower.(2) After knocking EZH2, we found that DAB2IP has a up-expression by using immunological imprinting.ConclusionsWe conclude that the result of EZH2 down-regualting DAB2IP in endometrial cancer cells HEC-1-B and RL-952, which may plays a role in the occur of endometrial cancer.