Effect Of Human Telomerase Reverse Transcriptase In Oncogenesis And Progression Of Renal Cell Carcinoma

Background and Objective:Renal cell carcinoma(RCC) is next most cancer in urological system. Surgery is the main method to treat RCC, while radiotherapy, chemotherapy and immumotherapy are uncertain. It is necessary to explore mechanism of RCC and find new method to treat RCC.Telomere, which defines the ends of chromosome, has close relationship with cell senescence and apoptosis. It has two main functions: one is to protect chromosome from degradation;and the other is end replication. Telomere replication needs a special enzyme human telomerase reverse transcriptase (hTERT), which always expressed in malignant cells rather than normal somatic cells. It is found hTERT promoter contains numerous Myc binding sites that mediate TERT transcriptional activation. So c-Myc has a direct role in induction of activity of telomerase, in which it preserves chromosome integrity by maintaining telomere length. Materials and methods:1. The study included 33 patients with renal cell carcinoma. After surgery, the tumor specimens and adjacent normal renal tissues were stored at — 80°C until use. The patient did not treat with chemotherapy or radiotherapy.2. Four tumor cell lines A498, KRC/Y, CAKI-2 and TK-10 were used in our study.3. Total RNA was extracted from the specimen and synthesized into cDNA. RT-PCR was performed to test the expression of hTERT and c-Myc.4. Telomerase activity was tested by using telomerase PCR Elisa Kit.Results:1. hTERT mRNA was detectable in 27 of 33 RCC samples, and all of them were hTERT -expressing tumors. All adjacent normal renal specimens expressed no hTERT transcripts regardless of the presence or absence of other hTERT mRNA variants.2. Twenty-seven of 33 tumors exhibited various degrees of telomerase activity. There are no relationships between telomerase activity and age of patient or gender. However, tumor size was significantly correlated with telomerase activation. Six of 12 RCC <5.0cm were negative for telomerase activity whereas none of 21 tumors >5.0cm lacked telomerase activity (PO.001, RCC <5.0cm versus >5.0cm).3. As the oncogene c-Myc is the key player in the activation of the hTERT gene, cDNA from 18 RCC specimens and corresponding normal tissues were available for c-Myc mRNA analysis. None of the 18 normal renal samples expressed detectable c-Myc mRNA. All 17 c-Myc -expressing tumors were positive for hTERT mRNA and telomerase activity.4. Telomerase activity and hTERT expression have close relationship with RCC development and progression.Conclusion:1. Telomerase activity expressed in renal cell carcinomas but not in normal renal tissue.2. hTERT mRNA expressed only in renal cell carcinomas but not in normal renal tissue.3. Close relationship between c-Myc induction and hTERT mRNA expression/ telomerase activation in renal cell carcinoma.4. Telomerase activation and hTERT mRNA expression has close relationship with oncogenesis and progression of renal cell carcinoma.