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The Role And The Regulation Mechanism Of Wnt In Tumorigenesisi And Development Of Cervical Cancer

Posted on:2016-07-22Degree:MasterType:Thesis
Country:ChinaCandidate:Y ChenFull Text:PDF
GTID:2284330464452995Subject:Gynecology
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Objective Cervical cancer is the number one malignant tumor threatened the life safety of women with a higher incidence. It presents an increasing state and the trend of younger age. The incidence of cervical cancer is a slow process. It need decades with a development from normal cervical tissues to cervical intraepithelial neoplasia, even cervical cancer. Early diagnosis and treatment of earlycervical cancer improve the treatment effect, the main strategy for quality of life and mortality. Cancer cells in the control and regulation will be involved in multiple signaling pathways, such as Hedgehog, Notch and Wnt etc. Wnt is a kind of development related conservative signal pathway, which has an important function for each system of the balance after the organization development. Wnt signaling pathway play an important role in the regulation effect of cervical cancer cell self-renewal and differentiation. Therefore, to explore the expression of Wnt in action during the occurrence and development of cervical cancer, it should be discuss that transferring of atransduction changes on Wnt signaling pathways in the genesis and development of cervical cancer, and even transfer to have very important role. Identification ofr Wnt provides theoretical basis for targets and treatmentstrategies in the mechanism of the occurrence and development of cervical cancer will be temporary bedtreatment of cervical cancer.Methods immunohistochemical Wnt-3a and beta-catenin protein detection in different cervical tissue edetermination method, the positive expression rates of Wnt-3a and-catenin protein were in abnormal expression rate. In order to analyze the correlation and clinical staging and pathological grading of cervical cancer, Wnt-3 and beta-catenin m RNA expression were detected by RT-PCR in human cervical carcinoma cell lines Hela, C33 A, Siha,Caski cells. Four kinds of cervical cancer cells expressed both the Wnt-3 and beta-catenin m RNA expression, except for the C33 A cells expressing slightly low,three cervical carcinoma cell lines Hela, Siha, Caski Wnt-3 and-catenin m RNA expression were more thanbeta relative expression quantity more than 1, suggesting that Wnt-3 and beta-cateninhigh expression in cervical cancer cells, the immune group and in human cervical carcinoma examination results are consistent. In order to change analysis on changes of Wnt and downstream cascade Road, different cervical tissue in liquid nitrogen grinding were analyzed using Western blot, level of p-m TOR, p-STAT3 and SOX2 protein expression in different tissues of the cervix analysis.Results 1) In normal cervical tissue almost no expression of Wnt-3a, Wnt-3a positive expression waslocalized in the cytoplasm, cytoplasmic expression of visible cervical intraepithelial neoplasia and cervicalsquamous cell carcinoma Wnt-3a protein positive expression in yellow, Wnt-3a positive expression rate is not very high. The positive expression of Wnt-3a in normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma rates were 10%(2/20), 35%(7/20) and 50%(15/30). The normalcervical tissues, the expression of cell membrane is continuous beta-catenin protein, the expression of brown, mainly distributed in spinous layer and basal layer of the epidermis cell membrane, cytoplasmwithout coloring; cervical intraepithelial neoplasia and cervical squamous cell carcinoma, cell membrane-catenin protein expression in the different degree of loss, even no expression, aberrant expression of beta-catenin mainly in the cytoplasm and the nucleus. The normal cervical tissues, cervical intraepithelial neoplasia and cervical squamous cell carcinoma beta the abnormal expression rate of-catenin were 15%(3/20), 50%(10/20) and 80%(24/30). In 30 cases with cervical cancer specimens, according to FIGO staging, I stage 16 cases, 8 cases of II stage, III stage 6 cases, the positive expression rates of Wnt-3awere 43.75%(7/16)、50.00%(4/8)and 66.67%(4/6); to compare between the three groups and compared between two groups were not significant difference beta, p>0.05; abnormal expression rate of-cateninwere 68.75%(11/16), 87.50%(7/8) and 100%(6/6), visible as the clinical staging, beta-catenin expressionincreased gradually, but between the three groups and compared between two groups were not significant difference, p>0.05. According to the pathological classification of 11 cases of grade G1, 14 cases of grade G2, 5 cases of grade G3, the positive expression rates of Wnt-3a were 45.45%(5/11), 42.86%(6/14) and 80%(4/5), to compare between the three groups and compared between two groups were not significant difference, p>0.05; beta-catenin positive rates were 63.64%(7/11), 85.71%(12/14) and 100%(5/5),visible with increasing grade of cervical cancer pathology, aberrant expression of beta-catenin increased gradually, and among the different pathological grades, butbetween the three groups and compared between two groups were not significant difference, p>0.05. 2) four kinds of cervical cancer cells can be seen in both the Wnt-3 and beta-catenin m RNA expression, except for the C33 A cells expressing slightly low, three cervical carcinoma cell lines Hela, Siha, Caski Wnt-3 and-catenin m RNA expression were more than beta relative expression quantity more than 1, suggesting that Wnt-3 and beta-catenin expression was higher in cervical cancer cells, immune group of this and in human cervical carcinoma examinationresults are consistent. 3) in cervical squamous cell carcinoma tissue expression of p-m TOR, p-STAT3 and SOX2 protein were significantly higher than those in normal cervical epithelial tissue and cervical intraepithelial neoplasia tissues and cervical intraepithelial neoplasia tissues of p-m TOR, p-STAT3 and SOX2 protein expression was significantly higher than that of normal cervical epithelial tissue.Conclusion The results indicate that Wnt signal pathway of beta-catenin expression were closely related to the occurrence and development of cervical cancer. Wnt signal pathway can be as additional markers for early diagnosis of cervical cancer, and activation of Wnt and beta-catenin abnormal expression may change with the m TOR-STAT3 signaling pathway. Abnormal expression of Wnt activation and beta-catenin via the m TOR-STAT3 pathway may offer therapeutic targets and treatment measures in preventing cervical cancer.
Keywords/Search Tags:cervical cancer, Wnt, beta-catenin, m TOR, STAT3
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