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The Antagonism Between Oncogene RMP And Tumor Suppressor PTEN In The Proliferation Of Hepatocellular Carcinoma Cells

Posted on:2016-06-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:S J YangFull Text:PDF
GTID:1224330464455029Subject:Medical Cell Biology
Abstract/Summary:PDF Full Text Request
Objective:The purpose of this study is to identify the different functions of oncogene RMP in hepatocellular carcinoma(HCC) cells and normal hepatic cells. The interaction and antagonism between PTEN and RMP have also been explored in the proliferation and apoptosis of hepatocellular carcinoma cells. Methods:1. Detecting the RMP m RNA and protein expression level in both various tumorcells and normal cells, and liver cancer tissues and the adjacent normal tissues.Testing the expression levels of HBX/AFP/BCL-2/BAX/BAD in the cancerand normal tissues. Analyzing the correlation between RMP and these factors.2. Determining the effect of RMP on the proliferation of various tumor andnormal cells through MTT. Detecting the influence of RMP on cellproliferation and apoptosis in HCC and normal liver cells.3. Comparing the expression of PTEN and RMP in HCC and normal liver cells.By Infection of liver cancer cells with the constructed PTEN adenovirusvector, exploring whether the exogenous PTEN inhibits RMP expression, andwhether PTEN regulates the effect of RMP on cell proliferation and apoptosis.4. Exploring the relationship between RMP and AKT signaling pathways bytreating the HCC cells with PTEN adenovirus vector and AKT signalingpathway inhibitor LY294002, respectively...5. Determining the influence of PTEN in xenograft model of human liver cancercells. Result:1. RMP has higher expression in tumor cells and tissues, compared to normalcells and tissues. AFP/HBX/BCL-2 are positively correlated with RMP, whileBAX/BAD are negatively correlated with it.2. RMP overexpression promotes the proliferation of tumor cells and normalcells, RMP depletion inhibits the proliferation of the tumor cells but not onthat of the normal cells.3. RMP depletion promotes the apoptosis of HCC cells, whereas no effect wasobserved on normal liver cell. Boost RMP expression may inhibit theapoptosis of Hep G2 cells,but not on SMMC – 7721,7702, or L02 cells.4. In contrast to that of RMP, the expression of PTEN is lower in HCC cells thanin normal liver cells. PTEN down-regulated RMP in a dose dependent manner.In HCC cells, PTEN inhibited the effect of RMP on cell proliferation, andapoptosis.5. PTEN reduced the expression of RMP by AKT signaling pathway, whichinhibits phosphorylation of BAD, inhibiting liver cancer cell proliferation.6. PTEN inhibits the promoting effect of RMP in generating transplantationtumor. Conclusion:RMP plays different roles in tumor cells and normal cells, with tumor cells sensentive to RMP and normal cells not. In HCC cells, the tumor suppressor PTEN down-regulated the expression of RMP by AKT signaling pathway and inhibited the RMP-induced proliferation of HCC cells.
Keywords/Search Tags:Hepatocellular
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