Functional Study Of Tumor-associate Gene Fibulin-5and Rasgrp2

In various human diseases, cancer is the "leading killer", it is a serious threat to human life and health. Cancer associated genes affect the emergence and development aspects of cancer, Oncogene to promote normal cells change to a cancerous cells, and suppress cancer genes are able to suppress cancer cell growth.Fibulin-5also called evec, dance, is the latest member of the ECM fibulin protein family.It plays t an important role in organs and vessels generation, fiber assembling and tumorigenesis. It was reported that Fibulin-5is specificly low-expressed in some tumor tissue after surgery, such as kidney, breast and colony. However, it is high-expressed in gastric cancer, the reason remains unknown. Our previous results showed that Fibulin-5could inhibit Hela cell proliferation and promote invasion, however, in the bladder cancer cell5637, Fibulin-5also inhibit cell proliferation but inhibit the invasion. All these refer that Fibulin-5’s function in tumor is tissue-specific.In this study, we for the first time systemly investigated the expression of Fibulin-5protein in the bladder cancer. Our results showed that Fibulin-5distingueshed high-expressed in the normal bladder tissue, but low-expressed in the tumor tissue. Meanwhile, this specific expreesion is associated with the tomor grade and stage:with the malignancy increasing, the expression of Fibulin-5becomes lower. This phenomenon is clearer in the bladder cancer cell lines.Next, we focused on the properly reason of the specificly expression. The bioinformation analysis suggests that there are intensive CpGs in the promoter of Fibulin-5. So we guess the DNA methylation might be the reason. The following MSP, BSP and5-AZA experiment confirmed it.We then investigated the function of fibulin-5in the bladder cancer. We found fibulin-5could distinguished inhibit the invasion of bladder cancer cell5637.We made further efforts to confirmed that in5637cell, fibulin-5could inbibit the expression of MMP7and MMP9, which could promote cancer cells invasion. All these results shoyed that fubulin-5inhibites5637cell invasion through inhibite the mmp7and mmp9expression.Finally, we researched on the infection mechanism of oncolytic virus mtHSV. We found Rasgrp2was a new interact protein of mtHSV. Rasgrp2is a dual Ras/Rap exchange factor, it could activate Ras. We found Rasgrp2regulated the infection of mtHSV to its nonpermissive cell NIH3T3from activating Ras. Rasgrp2is an oncogene; it could induce NIH3T3transforming to cancer cells from activating Ras. mtHSV could specificly infected cancer cells, so as the transformed NIH3T3.Above all, we researched on the function of two tomor-associated gene fibulin-5and rasgrp2. The expression and function investigation of fibulin-5in bladder cancer showed that fibulin-5may be a potencial diagnosis and therapy target in bladder cancer. The study of Rasgrp2provide further theoretical evidence that mtHSV may be used as an oncolytic agent for cancer therapy.