기초 : 뇌종양에서 진단적 지표로서의 Telomerase의 활성과 그 조절 기전에 관한 연구 = Study on the Activity and Regulation Mechanism of Telomerase as Diagnostic Marker in Brain Tumor

다국어 초록 (Multilingual Abstract)

Objective￡ºTelomerase is the ribonucleoprotein complex which elongates telomeric repeats(TTAGGG)n and appears to play an important role in cellular immortalization. The almost exclusive expression of telomerase in tumor cells, and not in most normal cells, offers an exciting opportunity for therapy by inhibiting its function. In order to know the possibility of telomerase activity as a diagnostic marker for prediction of prognosis in brain tumors, telomerase activity was investigated in and cell lines. Patients and Methods￡ºThe surgical specimens from 34 patients with of brain tumors were analyzed by TRAP assay for access telomerase activity. And the mechanism of regulation on telomerase activity in brain tumor was investigated by RT-PCR analysis of catalytic subunit of telomerase gene, hTERT, and c-myc oncogene in five cell lines. To investigate more factors involved in carcinogenosis in malignant brain tumors, gene expression analysis with Atlas human cDNA expression array was conducted in two glioblastoma cell lines, A172 and U373MG. Results￡ºMalignant brain tumors have high activity of telomerase. This means telomerase activity can be used as a marker for malignant brain tumor. The catalytic subunit of telomerase, hTERT, were coamplified with c-myc oncogene in brain tumors with high activity of telomerase. This finding suggest the possibility of c-myc as a regulatory factor on telomerase function. Atlas human cDNA expression array profiles of two cell lines showed common expression of 27 genes which were known as genes involve during carcinogenesis. Among 27 genes, there were four genes of cell cycle or growth regulators, one intermediate filament marker, three genes for apoptosis, two genes for DNA damage repair, three receptor genes, four genes for cell adhesion and motility, one gene for angiogenesis, one genes of invasion regulators, one gene belong to Rho family of GTPases, and seven genes of growth factors and cytokines. Conclusion￡ºThis study suggest that c-myc might be a possibile upstream regulator of telomerase activity in brain tumors and that 27 genes might involve the carcinogenosis of malinant brain tumor especially in glioblastoma.