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Expressoin Of E-cadherin, β-catenin And FAK In Colorectal Cancer And Their Clinical Significances

Posted on:2005-03-23Degree:MasterType:Thesis
Country:ChinaCandidate:W L WangFull Text:PDF
GTID:2144360125957378Subject:Digestive medicine
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Colorectal cancer is a kind of common and malignant tumor. The incidence of this disease has been increasing significantly in recent 20 years in China. The tumorigenesis and metastasis of colorectal cancer is a complicated process with many steps concerning the activation of oncogenes, inactivation of anti-oncogenes, the changing of adhesion among cells and the changing of activation of enzymes etc.E-cadherin (E-cad.) is a kind of crossing-membrace glucoprotein molecule, which, dependenting on calcium, establishes and holds homotypic cell adhesion and it is a kind of sliding fastener among homotypic cells. β-catenin( B -cat.) linked to E-cad.on cell membrace comes into being a kind of complex, which links to the actin in the cell framework through a-catenin.It is known that the homotypic cell adhesion, depending on the E-cad./ β-cat complex, plays an important role in the forming and maintaining of epithelial style.The factors which destroy this complex will breakdown the homotypic cell adhesion .Many clinic studies and experiments show that function of E-cad. always drops in most of cancers including colorectal cancer,breast cancer,prostate cancer etc. The cytoplasmic and /or nuclear expression of β-catenin may appear in the colorectal adenoma. β-cat. can link to the members of TCF/LEF family and stamp the transcription of some genes,which contributes to the tumorigenesis of colorectum.FAK(focal adhesion kinase) discovered by Schaller is a major substance which can be activated by src-ingeneration protein-tyrosine kinase and it is a non-receptorprotein-tyrosion kinase.It can regulate the developing, keeping alive, apoptosis of cells and adhesion between cells and ECM.It plays a role in the integrin-mediated signal transduction pathway through linking to the Focal Adhesion Foci.The activation of FAK is closely associated with its phosphptyrosine content and increases with its enhanced level of phosphotyrosine in colorectal cancer.The aim of this study is ,through evaluating the expression of E-cad., β-cat. and FAK in different colorectal mucosa and the relationship between their expression and clinicopathologocal factors,to provide theoretical basis for early diagnosis,therapy and prognosis of colorectal cancer.Materials and Methods:(1)49 surgically resected colorectal cancer samples,12 normal colorectal mucosa samples and 28 endoscopic resected colorectal adenoma samples with mild to moderate displasia were all confirmed pathologically. The samples in 2003 were fixed in 4% Polyoxymethylene/ 0.1M PBS (0.1%DEPC), and the rest were fixed in 10% neutral formalin. All the samples were embedded in paraffin. (2)SP immunohistochemistry technique was used to detect the expression of E-cad., β-cat. and FAK in the different colorectal mucosa.(3) The data was analysed by software SPSS 10.0. x2-test and spearman correlation were used to compare difference between groups, a =0.05 was considered as statistically significant value.Results: (1) The membranous expression of E-cad. appeared in most of nomal colorectal mucosa and colorectal adenoma.The reduced membranous expression of E-cad.appeared in a majority of colorectal cancer.The reduced membranous expression rate of E-cad. was 57.1% in colorectal cancer,which was significantly higher than the last two groups(P<0.01). The reduced membranous expression rate of 3 -cat. was 67.3% in colorectal cancer, which was significantly higher than the last two groups(P<0.01).The cytoplasmic and/or nuclear expression of β-catenin was found in the colorectal adenoma and cancer.The rate of the cytoplasmic and /or nuclear expression of β-catenin was 61.2% in coloretal cancer,which was significantly higher than that in colorectal adenoma(35.7%, P<0.05). Moreover, the rate of cytoplasmic and /or nuclear expression of β-catenin in colorectal adenomawas significantly higher than that in normal colorectal epithelium. FAK was expressed in cytoplasm.The rate of FAK expression was 65.3% in colorectal cancer, which was significantly higher than that in the colorectal adenoma...
Keywords/Search Tags:β-catenin, E-cadherin, FAK, Colorectal Cancer, Immunohistochernistry.
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