Sasgary, S. (2004). Telomere length regulation by telomerase in transformed and non-transformed rat cell lines: identification and characterization of the tert-gene and promoter from rat [Dissertation, Technische Universität Wien]. reposiTUm. https://resolver.obvsg.at/urn:nbn:at:at-ubtuw:1-11930
E166 - Institut für Verfahrenstechnik, Umwelttechnik und Technische Biowissenschaften
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Date (published):
2004
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Number of Pages:
161
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Keywords:
Telomerase; Enzymaktivität; Ratte; Zelllinie
de
Abstract:
Telomerase is a specific multi-subunit ribonucleoprotein that synthesizes TTAGGG telomere DNA onto chromosomal ends by using a RNA component (TERC) as a template for telomere specific sequences and the catalytic subunit (TERT). I was interested in the need for telomerase activity in self-developed immortalized and/or transformed cell lines derived from primary rat embryo cells (RECs). Therefore, a series of individual cell lines derived from RECs upon transfer of various oncogenes was analysed. Immortalisation of RECs by activated oncogenic c-Myc with or without a co-operating activated ras oncogene was clearly associated with very high telomerase activity. I established an oncogene inducible rat-cell-system (c-MycER/ras, c-Myc/MMTV ras und c-Myc/c-Ha-ras/mad1ER) and detected a positive regulation of the TERT gene by Myc proteins, whereas Mad proteins as known antagonist to Myc caused a negative regulation of the gene. Further, in silico techniques and partial genomic sequence data from rat genome project were used to clone the cDNA encompassing the complete rat TERT transcription unit and the core region of the rat TERT promoter. The effects of exogenous hTERT on telomerase activity and telomere elongation in a telomerase-negative background were investigated by transfection of the hTERT gene into suitable human lung cancer cell lines. The data indicate that ectopic telomerase expression and activity is capable to overcome individual telomere length regulation.