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The Preliminary Research Of Promoter Methylation Of The TSC2Gene In Endometrial Carcinoma

Posted on:2013-11-13Degree:MasterType:Thesis
Country:ChinaCandidate:M WangFull Text:PDF
GTID:2234330374959145Subject:Obstetrics and gynecology
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Objective:Edometrial Carcinoma (EC) is one of the most commonmalignant tumor in the female reproductive, accounting for about7%of thetotal women cancer, and accounting for about20%to30%of the femalereproductive tract malignant tumor. ECs are a group of epithelial malignanttumors, and most are of the endometriold histologic subtype, high-risk age60to65years old. The prognosis were good, because the lesions were limited inthe uterus when be diagnosised. Nearly20years,ECs incidence risedsignificantly, and the patients under the age of45increased. Tuberoussclerosis (TSC) is one of the neurocutaneous syndromes characterized bysebaceous glands, seizures and intelligence drops, and is an autosomaldominant disorder that results from mutations in the TSC1or TSC2genes. TSC1/TSC2genes lie at9q34/16p13.3, and encode hamartin/tuberin, respectively.Tuberin and hamartin are coexpressed in most human tissues, and they form acomplex-TSC1/TSC2complex, of which tuberin may act as a chaperone,preventing self aggregation of hamartin via its carboxyl-terminal coiled coildomain in cytoplasm. PI3K/Akt/mTOR signaling pathway is often activatedin human malignant tumors. TSC1/TSC2complex acts to inhibit mTORsignaling. When hamartin/tuberin disexpressed because of some causes,mTOR signaling is activated, initiating tumor. Methylation of DNA which isthe research hot spot today, is one form of modifying in epigenetics. Thenomal methylation of DNA play important roles in maintaining the function ofthe body, but the abnomal may be related to many diseases, especially somechronic diseases be bound up with age, such as type II diabetes, autoimmunedisease and tumors. Methylation of DNA is one of the inactivationmechanism of tumor suppressor gene, and it play important roles in the occu-rrence and develpment of tumors. In this study,we examined the frequency of methylation of TSC2gene, in order to disscuss the roles of the promoter ofTSC2gene in the occurrence of edometrial carcinoma.Methods:The30specimens of endometrial cancer were collected fromthe patients with endometrial cancer after being panhysterectomy or diagnosticcurettage,at the Department of Obstetrics and Gynecology in NumberThree/Four Hospital of Hebei Medical University from September2009toSeptember2011. The30specimens of nomal were obtainted from patientsneed operation because of myoma of uterus or uterine prolapse, at theDepartment of Obstetrics and Gynecology in Number Three Hospital of HebeiMedical University. All specimens were diagnosised by experiencedpathologists, and were saved in-800C. Genomic DNA of all the specimenswere extracted by phenol-chloroform-isoamyl alcohol, and the promotermethylation state of the TSC2gene were detected by MSP. Statistical analysiswas performed using the Statistical Package of Social Science13.0forWindows. Differences between groups were analyzed by the chi-square. Pvalues less than0.05was considered statistically signicant.Results: The promoter methylation of the TSC2gene was not detected innomal endometrial tissue, and the frequency of the methylation was0.Whereas the frequency of the methylation of TSC2gene in endometrial cancerwas23.3%(7/30).There are significant diversity between them(P<0.05).Conclusion: Promoter methylation of the TSC2gene might playimportant role in the occurrence of endometrial carcinoma.
Keywords/Search Tags:Edometrial Carcinoma, TSC2, Tuberin, Methylation, Methylation-specific polymerase chain reaction
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