| Bladder cancer is the most common malignant neoplasm in the urinary system, which is high incidence and recurrence rate. About 95% of bladder cancer is the transitional carcinoma cell of the bladder (TCCB). The traditional diagnostic method of TCCB is cystoscopy, which is invasive examination and can not find the early pathological changes. The therapy of TCCB is combining surgical operation with chemotherapy perfusion in the bladder, which has many adverse effects and high recurrence rate. Therefore, the effective method of improving TCCB survival rate is to seek for non-invasive, sensitive and specific, early diagnostic markers and to apply the new high-effective and low-poisonous therapeutic tools. Be similar to most malignant neoplasms, the immortalization of TCCB cells is close relationship with telomerase and telomere of the end of chromosome. It has been studied that telomerase was composed of human telomerase RNA (hTR), telomerase related protein 1(TLP1/TP1) and human telomerase reverse transcriptase (hTERT). Among them, hTERT, also called telomerase catalytic subunit, is the rate-limiting factor of telomerase activity and the determinant factor of telomerase activation. Except for hemopoietic progenitor cells, spermatogenous cells and oocyts, there was no expression of hTERT in other somatic cells. It was reported that the relationship between hTERT and malignant neoplasm was closer than that between telomerase and tumors. Meanwhile, expression of hTERT is related to c-myc expression in tumor cells. The transcript regulation of hTERT was affected by various factors in tumor cells. Especially the expression product of c-myc and mad1, which contain basic helix-loop-helix structure domain, could bind with E-box(CACGTG)sites of hTERT promoter to regulate hTERT transcription. Both c-myc and mad1 gene could regulate tumor cell proliferation, differentiation and apoptosis through the pathways of cell cycle. The double influence of cell growth by c-myc was existed, and the effects of c-myc gene were determined by the combining gene character. It would cause cell proliferation when combining with proliferation-promoting genes, otherwise cause cell apoptosis or necrosis. Mad1 protein is the mitosis checkpoint protein, which increased the amount during the cell phase of G0 G1 conversion, stagnated cells at G1 phase to accelerate cell differentiation. According to some studies in other malignant neoplasm, the possible mechanisms of hTERT transcript regulation by c-myc and mad1 were considered as follows: First, c-myc and mad1 gene could activate and inhibit TGF-β1 gene respectively, further to activate Smad signal transduction pathway and regulate hTERT transcription. Second, c-myc and mad1 gene could increase the amount of SID-mSin3A complex to activate EGF-Ras-MEK1-ERK2 pathway in cells to mediate hTERT transcription and telomerase activation. Third, c-myc and mad1 gene could combine with suppressor P53 gene to regulate hTERT transcription and further affecting cell proliferation or cell apoptosis. Fourth, c-myc and mad1 gene could regulate hTERT expression with histone diacetaminase complex (HDAC), acetylated and diacetylated of histone. Fifth, c-myc and mad1 gene could bind with co-repressors mSin3 and mSin4 to affect the conformation of hTERT promoter to regulate its transcription.Nowadays, hTERT was selected as therapy target of malignant neoplasm because it high selectively expressed in cancer cells but not in most somatic cells.hTERT promoter guiding effective genes could targetly kill malignant cells but no effects on normal cells because hTERT only expressed in tumor cells while no expression in most normal somatic cells. It was reported that hTERT promoter guiding suicide genes and apoptotic genes limited the effects on telomerase positive tumor cells, while no effects on telomerase negative cells, which improved the safety of gene therapy for tumors. Some research reported that inhibition of hTERT expression could change the malignant phenotype...
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