Dissertation
Dissertation > Medicine, health > Internal Medicine > Systemic disease > Genetic diseases > Chromosomal diseases

The Key Members of Classical Wnt Singal Pathway Expression in the Polyp Tissue of Peutz-Jeghers Syndrome

Author LuXiangJi
Tutor GuGuoLi
School Hebei North University
Course Human Anatomy and Embryology
Keywords Peutz-Jeghers disease β-catenin epithelial cadherin matrixmetalloproteinases-7 C-myc cyclin D1 immunohistochemistry
CLC R596.1
Type Master's thesis
Year 2013
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Peutz-Jeghers syndrome (Peutz-Jeghers syndrome, PJS) is a by LKB1/STK11germline mutations cause autosomal dominant genetic disease. Caused intussusception, bleeding, obstruction, malignant polyps and severe concurrent disorders cause patients to be repeated hospitalization. The present study only to determine the genetic cause of PJS but LKB1/STK11mutations lead to the the PJS onset of the specific mechanism is not clear. And the current the PJS polyp clinical treatment with surgery, passive means supplemented by endoscopic resection. These means can only temporarily delay the polyps, can not achieve the purpose of the development of prevention polyps. Many PJS patients often fall into the plight of the polyp repeated treatment was repeated growth, eventually malignant metastasis and deadly. Study found:a variety of cellular signaling pathways may the PJS polyps occur development. PJS polyps abnormal cell signaling pathways to be blocked, it is possible to suppress the occurrence and development of PJS polyps. Wnt signaling pathway is an evolutionary highly conserved embryonic development, regulation of cell growth and proliferation has an important role in the transduction pathway. Involved in gene transcription, cell cycle, cell proliferation, apoptosis and other biological activities. Abnormal activation plays an important role in embryonic development and tumorigenesis, development of key physiological and pathological processes much of the majority of the attention of scholars. The study found that:the canonical Wnt signaling pathway plays an important role in the process of tumor biology; research articles in PJS polyps rarely reported. Study by the the explicit canonical Wnt signaling pathway key members-epithelial cadherin (E-cadherin, E-Cad),(3-catenin (β-catenin, β-Cat), cyclin D1(Cyclin Dl), matrix metalloproteinase-7(Matrix Metalloproteinase-7, MMP-7), human c-myc oncogene product (C-Myc) expression in PJS polyps state to explore occur in PJS polyps, role in the development process; Wnt pathway inhibitor for PJS polyps targeted therapy provide a theoretical basis.Experiment, randomly selected from the experimental group of2010/06-2012/06during the Air Force General Hospital surgical treatment, Gastroenterology small intestine endoscopic treatment of40cases of PJS patients, all cases in line with the the National Hereditary colorectal cancer collaborative group to develop the PJS diagnosis standard, randomly selected from the same period20patients underwent radical surgery in patients with colorectal cancer positive control group,20healthy people selected in the outpatient colonoscopy negative control group.Immunohistochemical staining to detect the PJS polyps organization (n=40), and protein expression in colorectal carcinoma (n=20) and normal intestinal mucosa (n=20) in five organizations December slice, dewaxing to the water. E-Cad,β-Cat, Cyclin D1, C-Myc, MMP-7do not need to deal with hot fix after antigen. Unmounted in phosphate buffered saline (PBS) as negative control instead of primary antibody, known positive sections as a positive control.The positive expression rates of E-Cad,β-Cat in membrane,β-Cat in nucleus, MMP-7, C-Myc and Cyclin D1were significant differences among the normal mucosa group(χ2=48.13, P<0.01; χ2=55.98,P <0.01;χ2=52.80, P<0.01; X2=44.14, P<0.01;χ2=27.37, P<0.01; φ2=40.44, P<0.01), PJS group and colorectal cancer group. In the PJS group, the expression of E-Cad and β-Cat in membrane increased following of the age increasing and size enlarging; and the expression of β-Cat in nucleus, MMP-7, C-Myc and Cyclin D1increased following of the polyp size enlarging. Result prompt:The positive expression rates of E-Cad, β-Cat in membrane, β-Cat in nucleus, MMP-7, C-Myc and Cyclin D1were significant differences among the normal mucosa group may be owing to PJS canceration. PJS group and colorectal cancer group. In the PJS group, the expression of E-Cad and(3-Cat in membrane increased following of the age increasing and size enlarging; and the expression orβ-Cat in nucleus, MMP-7, C-Myc and Cyclin D1increased following of the polyp size enlarging. The expression of E-Cad and β-Cat in membrane had a negative correlation withp-Cat in nucleus, MMP-7, C-Myc and Cyclin D1in the polyp tissue of PJS. It’sbecaues of PJS polypous formation and The aberrant activation of classical Wnt pathwayclosely.

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