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The Expression and Significance of Twist、 E-cadherin and P53 in Cervical Cancer

Author: ChangLei
Tutor: LuAiNi
School: Zhengzhou University
Course: Obstetrics and Gynaecology
Keywords: Cervical squamous cell carcinoma Twist E-cadherin P53 Immunohistochemistry
CLC: R737.33
Type: Master's thesis
Year: 2011
Downloads: 50
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Abstract


Background and purpose: cervical squamous cell carcinoma is the most common female malignancy, accounting for more than half of the female reproductive system cancer;, it is a serious threat to women's quality of life, health and life, the mechanism of the occurrence of cervical squamous cell domestic and foreign scholars in the ascendant. The pathogenesis of cervical squamous cell protein levels, clinical diagnosis, differential diagnosis and guide clinical treatment, has a very important significance. Twist in experiments on Drosophila first identified it to play an important role in a range of the growth process, especially in the generation of the initial stage of mesoderm particularly evident. 1996, Twist gene was cloned, located on human 7p21.2 In point contains two exons and an intron, encoding 203 amino acids, a molecular mass of about 28 kd. Twist gene contains the basic helix - loop - helix family (basic Helix-Loop-Helix family, bHLH) Twist gene and with other species or heterologous bHLH gene fusion, two DNA fragments were combined into a domain, in a special way The combination and the E-box, this can special upward or interfere with the process of transcription of the target gene. E-cadherin (E-cadherin protein) is a very important adhesion molecules, is a single transmembrane glycoprotein, and the maintenance of the epithelial type. Each other through intermolecular the cell outside immunoglobulin domain to establish contact, and through the α, β-catenin and muscle actin cytoskeletal connection, thus the formation of cell binding. Inter-adsorbing function in the absence of the factor of the E-cadherin cell decreased or disappeared, sticking to each other and the ability of cells is reduced, thereby enabling the separating malignant cells from the primary lesion, metastasis to other organs are found in most malignant on. Epithelial cell mesenchymal transition (epithelial-mesenchymal transition, EMT) embryonic development, chronic inflammatory response, as well as a major stages of tumor progression, occupies a significant position in the stage of development of most malignant tumors EMT. Its distinguishing feature is the epithelial cell polarity disappear and the characteristics of the interstitial invasion and metastasis of cancer cells have a major impact. The experiment, as part of the bHLH family, Twist can impact upstream of the process of synthesis of E-cadherin, interfere with its transcription and binding process, making cancer the increased possibility of further deterioration. EMT in the embryonic generation process plays an important role, it can serve as the beginning of the deterioration of malignant cells. At the transcription stage, Twist role in the E-box sequence initiation factor that may produce the EMT process leading to E-cadherin is disturbed. The study found, Twist is a new type of cancer gene, it can interfere with the physiological death of cells, this process involves P53 dependent and non-dependent channel. Twist-siRNA can promote its very lack of P53 in breast cancer and melanoma cell lines apoptosis, reduction in the number of prostate cancer study found that Twist can make cells more likely to apoptosis, which is due to the cancer itself is missing P53 to arrive Twist P53 channel can be used to adjust the programmed death of cells. The experimental progress, Twist upregulation of great significance to the development of cancer, as well as the deterioration of the process, clear the mechanism is still not clear. Twist expression in cervical squamous cell upregulation and decreased cancer progression and deterioration remains for further study and discussion. Based on the above discussion, this study using immunohistochemical methods to detect Twist and E-cadherin and P53 three related gene expression in cervical tissue, analysis of the abnormal expression of Twist, E-cadherin and P53 in cervical squamous cell development of mutual relations, and the correlation of expression between the three factors analysis, explore the Twist, the relationship between E-cadherin and P53 protein expression and clinicopathological parameters, further the pathogenesis of squamous cell carcinoma of the uterine cervix elaborated, as basis for the development of cervical squamous cell carcinoma, invasion and metastasis research. Materials and Methods: collected cervical tissue in the period December 2009 to April 2010, the Second Affiliated Hospital of Zhengzhou University, Department of Pathology, a total of 150 cases, including 50 cases of chronic cervicitis tissues, cervical intraepithelial neoplasia (CIN) organization (cervical intraepithelial neoplasia, CIN ) 50 cases (CIN Ⅱ grade 22 cases, CIN Ⅲ grade 28 cases), 50 cases of cervical squamous cell. Twist in the detection of human chronic cervicitis tissues using immunohistochemical method (SP method), cervical intraepithelial neoplasia (CIN) organizations and cervical squamous cell carcinoma of E-cadherin and P53 protein expression, and data results application SPSS11.0 statistical software package for statistical analysis, α = 0.05 level of inspection. : 1.Twist, E-cadherin and P53 expression in cervical tissue positioning: immunohistochemical staining Twist protein displayed positive staining in the cytoplasm; E-cadherin protein in the cell membrane and (or) cytoplasmic positive staining; P53 protein showed positive staining of nuclei. 2.Twist, E-cadherin and P53 expression in cervical tissue strength: Twist and P53 protein expression in cervical squamous cell strength than chronic cervicitis and cervical intraepithelial neoplasia (CIN); E-cadherin protein in cervical squamous cell carcinoma The expression intensity lower than the chronic cervicitis and cervical intraepithelial neoplasia (CIN). 3.Twist, E-cadherin and P53 in cervical tissue expression rate: Twist protein levels are higher than in cervical squamous cell chronic cervicitis and cervical intraepithelial neoplasia (CIN), with statistical significance; chronic cervicitis and cervical intraepithelial neoplasia (CIN) group between Twist expression levels with no significant difference. E-cadherin protein expression levels in cervical squamous cell carcinoma than in chronic cervicitis and cervical intraepithelial neoplasia (CIN), with statistical significance, no significant difference in the level of expression of E-cadherin and chronic cervicitis and cervical intraepithelial neoplasia (CIN) group comparisons . P53 protein from chronic cervicitis, cervical intraepithelial neoplasia (CIN) to the level of cervical squamous cell expression gradually increased, with statistical significance. 4.Twist relationship between E-cadherin and P53 protein expression and clinicopathological parameters: Twist protein expression levels in different clinical stages of cervical squamous cell carcinoma, lymph node metastasis and statistically significant comparison between different pathological differentiation. E-cadherin protein expression levels in different clinical stages of cervical squamous cell carcinoma and pathological differentiation between statistically significant and in the lymph node metastasis, there was no statistical difference between the positive and negative groups. P53 protein expression levels in different clinical stages of cervical squamous cell carcinoma and pathological differentiation between statistically significant and in the lymph node metastasis, there was no statistical difference between the positive and negative groups. Twist protein expression of E-cadherin in cervical squamous cell correlation analysis between the P53: negative correlation between the the Twist expression of E-cadherin; Twist positive correlation between protein expression and P53. Conclusion: 1.Twist protein may be involved in the development and progression of squamous cell carcinoma of the uterine cervix, reflect the degree of malignancy of cervical squamous cell and squamous cell carcinoma of the uterine cervix invasion and metastasis have a certain influence. 2.E-cadherin protein may be an important indicator of clinical treatment and assessment of prognosis. 3.P53 proteins play an important role in the mechanism of occurrence of squamous cell carcinoma of the uterine cervix. 4.Twist protein may affect both the P53 and E-cadherin, induce the development of cervical squamous cell carcinoma metastasis invasion.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Female genital tumors > Uterine tumors
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