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The Expression Of Mdm2, Pten And P53 Protein In Esophageal Squamous Cell Carcinoma And Its Relationship

Posted on:2010-03-15Degree:MasterType:Thesis
Country:ChinaCandidate:E N LiuFull Text:PDF
GTID:2194360302976232Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
so far P53 is a tumor suppressor gene which is studied most widely.The product of P53 gene is a kind of phosphoprotein,which located in cytoblast and belongs to cell cycle associated protein.P53 protein can bind DNA sequence specifically and activate some genes,which can participate in regulating cell cycle and suppress abnormal cell into S cycle and induce cell apoptosis and inhibit expression of some genes that are related with cell malignant proliferation,and suppress angiogenesis and inhibit metastasis of tumor cells and so on.P53 protein has wild type and mutant type. Wild type p53 protein expresses lower in all normal cells,while mutant type P53 protein expresses higher in tumor cells.The mutation of p53 gene always ascribes to the occurrence and development of tumor.MDM2(murine double minute 2) protein,as a DNA binding protein,represses wild type P53 to inhibit cell transformation and possessing transcription and regulation.The biological role of MDM2 can strengthen cell longevity,extending cell life span,facilitating cell proliferation and tumor growth.The research showed that the function of MDM2 is correlated with P53.Activated P53 leads to excessive expression,while the expression of MDM2 suppresses gene expression of wild type P53.MDM2 could be expressed or proliferated in malignant tumors such as soft-tissue sarcoma,bladder carcinoma and so on.Studies indicated that PTEN(phosphatase and tension homology on chromosome ten) is at present one of tumor suppressor gene,which has activity of lipid phosphatase.PTEN protein is a multifunctional protein and is able to inactivate its substrate(PIP3),which is dephosphorylated.The deprivation of the phosphatase activity can lead the genesis,development and metastasis of tumor.Growth inhibitory activity of PTEN is relevant to cell growth and apoptosis,regulating migration of cell and cytoskeleton formation.The research showes that PTEN gene mutates in human existed in many kinds of tumors and hereditary tumor sensitive syndrome and so on. The expression of PTEN is also relevant to prognosis of tumor patients.At present the research of PTEN has been a hot spot in tumor genesis,metastasis and prognosis and SO on.To update,the expression of MDM2,PTEN and P53 protein in esophageal squamous cell cancer(ESCC) and its relationship have a few relevant reports.In order to explore the mechanisms of ESCC which can sustain early diagnosis,early treatment of ESCC and lower morbidity and mortality of ESCC,our research adopted immunohistochemistry method,detecting the expressions of MDM2,PTEN and P53 protein in ESCC tissues of 67 cases,adjacent atypical hyperplasia tissues of 34 cases and normal mucosa tissues of 33 cases.Our research explores further the mechanisms of occurrence,development of ESCC and provide rationale for early diagnosis,early treatment.Methods1.Using the immunohistochemistry SP to detect the expression of MDM2, PTEN and P53 protein in the 67 cases ESCC,34 cases of atypical hyperplasia tissues of tumor-adjacent and 33 cases of normal mucosa of ESCC.2.Statistical analysis:All the dates were analyzed by SPSS 13.0 statistical package for windows.The count data was calculated the positive rate.The comparison of positive rates were analysied by using theχ~2(chi-square);The relation of two variable were analyzed by the spearman correlation analysis.The level of significant difference isα=0.05..Results1.Immunohistochemical results showed:The positive expression rates of the three targets in normal mucosa,atypical hyperplasia tissues and the carcinoma tissues showed significantly difference.The positive expression rates of MDM2 protein were 0%(0/33),23.53%(8/34) and 50.74%(34/67),respectively;The positive expression rates of P53 protein were 6.06%(2/33),26.47%(9/34) and 61.19%(41/67), respectively;The positive expression rates of PTEN protein were 93.94%(31/33), 61.76%(21/34) and 38.81%(26/67),respectively.The positive expression rates in each two groups showed significance(P<0.05).2.In the tissues of ESCC,the positive rates of expression of the three proteins on the low-muscle invaded,deep-muscle invaded and outer layer invaded showed as follows:The positive expression rates of MDM2 protein were 15.00%(3/20),50.00% (12/24) and 78.26%(19/23),respectively;The positive expression rates of P53 protein were 20.00%(4/20),66.67%(16/24) and 91.30%(21/23),respectively;The positive expression rates of PTEN protein were 75.00%(15/20),41.67%(10/24) and 8.70% (2/23),respectively.The positive expression rates in each two groups showed stastical significance(P<0.05).3.Immunohistochemical results indicated:In the 33 cases of lymphonodus metastatic group and the 34 cases of non-metastatic group,the positive rates of expression of the three proteins in the tumor tissues appeared as follows:The positive expression rates of MDM2 protein were 63.64%(21/33) and 38.24%(13/34), respectively;The positive expression rates of P53 protein were 75.76%(25/33) and 50.00%(17/34),respectively;The positive expression rates of PTEN protein were 24.24%(8/33) and 52.94%(18/34),respectively.There was significant difference between each two groups(P<0.05).4.The mutual correlation of the expression of MDM2,P53 and PTEN in esophago squamous carcinoma was analyzed.The results showed that the both former were also negative correlation with the later(P<0.05),There was a positive correlation between former both(P<0.05).Conclusions1.It indicated that MDM2,P53 and PTEN participated in occurrence and development of ESCC. 2.It indicated that MDM2,P53 and PTEN participated in infiltration of ESCC.3.It indicated that MDM2,P53 and PTEN participated in metastasis of ESCC.4.Relativities of the expression of MDM2,P53 and PTEN protein were analysized by statistics,Results showed relative and they played synergistic effect during the process of occurrence and development of ESCC.
Keywords/Search Tags:esophageal squamous cell carcinoma(ESCC), MDM2, P53, PTEN, infiltration, metastasis
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