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Expression Of Human Telomerase Reverse Transcriptase And Its Correlations With Cell Apoptosis And Proliferation And C-myc In Hepatocellular Carcinoma

Posted on:2004-08-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:S G LiFull Text:PDF
GTID:1104360092990627Subject:Surgery
Abstract/Summary:PDF Full Text Request
Hepatocellular carcinoma(HCC) is one of the common malignant tumors in our country and its mortality has risen to the second position in all the neoplasms', which owns malignant behavior including rapid metastasis, fast development and transient free -tumor survival. Through half of a century working hard, many achievements have been obtained at the operative treatment in HCC, but the therapeutic results of traditional operation combined with chemotherapy or radiotherapy are limited. Relapse after radical resection occurs frequently. Hence, it is an effective way for improving the therapeutic result in HCC to study molecular biology in HCC and explore a new approach in tumor biology therapy.Discovered in 1997, human telomerase reverse transcriptase (hTERT), as a homologue from Tetrahymena p128, is a one-copied gene and one of core sections composed of telomerase activity. By transfecting it into telomerase-negative cell, hTERT effectively reactive telomerase activity and restore cell proliferation. hTERT expression is a rate-limiting factor of telomerase activity. And so, the study on hTERT expression helps to comprehend the mechanism of telomerase. At present, it is not understood how hTERT expression influences HCC. It is thought that hTERT expression is a very reliable marker of early diagnosis of HCC, especially ofthe small difficult- diagnosed HCC and the AFP-negative tumor, but strong hTERT expressions were detected using in situ hybridization in normal liver tissues. The discrepancy is unclear. The positive relations of hTERT expression and the clinicopathological features of HCC are uncertain. Negative correlation between the expression strength of hTERT and the dedifferentiation of HCC decides the correlation between the expression of telomerase activity and the degree of tumor' s histologic differentiation, while other research doesn't support the viewpoint. There stands reverse point about its relation with the size of rumor,what is more, the correlation between the hTERT expression and the other clinicpathological features was not discovered. These undetermined factors must bring effects to the utilization of hTERT gene in diagnosis and treatment of HCC.There is a close relationship between tumor proliferate behavior and the transcriptase level of c-myc gene. Research shows that transcription activity can be brought to the full play only under the condition that it structures a heterodimers by combined with Max which has the identical bHLH-Zip structure . Several c-myc binding sites of hTERT promoter hint that it is possible that c-myc is the regulation factor of hTERT expression, which has been proved by other tumor research. However, the expressions of telomerase and hTERT in the HCC cell lines have been declined after drug action, and the expression of c-myc gene has not been variance, this illustrates that the discrepancy of the mode in which c-myc affects hTERT activity lies in the different population. At present, there is not the investigation on the relation between hTERT and c-myc in the tissues of HCCIn order to maintain cells amount stable, well-functioned body state and clear abnormal cells, dynamic equilibrium of cell apoptosis and proliferation must be achieved, the failure of which will lead to the occurrence of tumor directly. The nov-activation of telomerase activity is closely correlatel with the dysequilibrium of apoptosis and proliferation. In vitro experiment shows telomerase activity competence suppression will cause to shorten constantly telomere length, suppress cell growth and increase apoptosis.Telomerase is primarily expressed in the majority tumors. Telomerase expression in thetissues is highly concordated with the proliferate-related antigen Ki-67 expression which reflects cell proliferation behavior. hTERT is the key factor of telomerase activity and its expression accords with telomerase expression. So it postulates that hTERT expression could be related to cell proliferate and apoptosis, which has been confirmed in other tumor tissues. Pre...
Keywords/Search Tags:hepatocellular carcinoma, human telomerase reverse transcriptase (hTERT), c-myc, apoptosis, proliferate, Clinical pathology
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