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Study On The Relationship Between MRNA And Protein Of Twist, E-cadherin, N-cadherin Genes And Gastric Cancer

Posted on:2010-02-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:S K HongFull Text:PDF
GTID:1114360275965449Subject:Surgery
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Background and objective:Twist was originally identified in Drosophila as a protein involved in the regulation of diverse developmental processes, particularly in the formation of mesoderm.The human Twist gene is located at chromosome 7p21.2.The Twist protein consists of 201 amino acids and its molecular weight is about 28kd.Twist protein is a transcription factor that belongs to the family of basic helix-loop-helix(bHLH)protein.The mechanism of bHLH molecules require that they either homo-or heterodimerize with other bHLH molecules,form a bipartite DNA-binding domain and bind to a conserved E-box region on the promoter of genes which activate or inhibit transcription.Recent studies have shown that Twist is a potential oncogene and be involved in the protection of apoptosis via both p53-dependent and independent pathways.To date several studies revealed that Twist played crucial roles in tumorigenesis, invasion and metastasis,but its accurate molecular mechanisms remain unclear.However,there have been little available data on the role of Twist in the development and progession of gastric cancer;the molecule involved in the regulation of Twist and its mechanism was still unclear. We researched for the molecule involved in the regulation of Twist and its mechanisms.Epithelial-mesenchymal transitions (EMT) is a process that epithelial cell layers lose polarity and acquire expression of mesenchymal components and manifest a migratory phenotype. It exists in many physiological and pathological p rocesses in human body. The progress of EMT involves a number of signal transduction pathways and complex molecular mechanisms, and is related to calcium catenin,growth factors, transcription factors, microenvironment, and so on. EMT play an important role in tumor metastasis. E-cadherin and N-cadherin are members of the family of transmembrane glycoproteins expressed on epithelial cells and are responsible for calciumdependent cell -to-celladhesion. E-cad can lead to Loss of cell adhesion,cell adhesion may contribute to loss of contact inhibition of growth, which is an early step in the neoplastic process.Furthermore, loss of cadherin activity may result in cancer cell detachment and metastasis.It has been suggested that, unlike E-cadherin, N-cadherin may promote invasion and metastasis of carcinoma. Twist,E- and N-cadherin are important molecules that modulate cell migration and tumor,invasion.According to above metioned consider, in this study, Reverse transcription polymerase chain reaction (RT-PCR) technique and immunohistochemical method were used to detect the expression of Twist,E-cadherin and N-cadherin in gastric cancer. So that to provide experimental evidence for elucidating the etiopathogenesis, treatment and prevention in gastric cancer.Methods:1 .Reverse transcription polymerase chain reaction (RT- PCR) technique was used to examine the expressions of Twist,E-cadherin and N-cadherin mRNA in the 58 gastric cancer tissues and their 58 non-tumorous gastric tissues.2. Supervision TM immunohistochemical method was used to detect the expression of Twist,E-cadherin and N-cadherin proteins in 58 cases of gastric cancer tissues and their non-tumorous gastric tissues.3. SPSS 10.0 statistical software was applied to statistics the date. To categorical variable the sperman correlation analysis were used to analyze. To numerical variable the date was expressed with x士s and t test was used to compare these datas. The significant level was a =0.05.Results:1 .The positive expression of Twist,E-cadherin and N-cadherin locate in land 210bp,132bp,156bp. The positive expression of Twist,E-cadherin and N-cadherin mRNAs were 72.41%,39.66%, 48.28% in gastric cancer tissues, and were 31.03%, 84.48%, 13.79% in non-tumorous gastric tissue, respectively. (P<0.01).2. The positive expression rates of Twist,E-cadherin and N-cadherin proteins were 75.9%,36.2%,44.8% in gastric cancer tissues, and were 32.8%,91.3%,12.1% in non-tumorous gastric tissue,respectively. (P<0.01).Conclusions:1 .The higher expressions of Twist,N-cadherin and the lower expression of E-cadherin in gastric cancer had the close relation to carcinogenesis of gastric cancer.2. The expressions of Twist,E-cadherin and N-cadherin are related with the invasion,metastasis of gastric cancer,the genes of Twist,E-cadherin and N-cadherin participate with process of EMT together. 3.United measurement of the expression of Twist,E-cadherin and N-cadherin genes is helpful to predict metastasis of gastric cancer and to judge prognosis of gastric cancer.
Keywords/Search Tags:Gastric cancer, Twist, E-cadherin, N-cadherin, Metastasis, EMT
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