TELOMERASE · Identification and functional assessment of genes specifically involved in hTERT regulation
6РП — Действия „Мария Кюри“
- Период
- 2005-02-01 → 2007-01-31
- Финансиране от ЕС
- 21 500 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Генните фактори, които контролират активността на ензима теломераза, се анализират чрез промяна на тяхното количество в левкемични клетки. Това помага за разбирането на процесите, при които раковите клетки стават безсмъртни и се развиват тумори.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - TELOMERASE (Identification and functional assessment of genes specifically involved in hTERT regulation)
Telomerase, an enzymatic complex responsible for the maintenance of telomeres, is significantly expressed in 90% of cancer cells and apparently absent in normal somatic cells. Expression of the protein component of this telomerase complex, human Telomerase Reverse Transcriptase( hTERT), seems to be the limiting factor for telomerase activity, and plays a fundamental role in cellular immortalisation. The knowledge of the factors and mechanisms controlling hTERT gene expression is highly significant to understand the telomerase re-activation process, a key step during tumourogenesis in human cancers. At this date, only few transcriptional factors able to bind the promoter of hTERT gene have been described in the scientific literature and their genuine contribution in telomerase regulation has not been demonstrated yet. Moreover, published data from different laboratories indicate that important relevant transcription factors have not yet been identified. Thus, the factors and mechanisms controlling the hTERT transcription still remain to be elucidated during physiological processes. This project, funded by a Marie Curie EIF during two years (University of Bergen, Norway), has allowed the identification of eight transcription factors rapidly induced by retinoids (vitamin A derivatives) and potentially important in telomerase regulation. These eight transcription factors, early-induced by retinoic acid, have been identified by a microarray approach (DNA biochips) and their expression confirmed with different techniques of biochemistry and molecular biology. Our goal is now to assess the contribution of these eight candidate genes in telomerase regulation leukemic cells, by studying the consequence of their over-expression and/or specific invalidation (by RNA interference). All the molecular and cellular tools required for the functional study of these candidate genes have been developed in the perspective of my reintegration in France (also granted by a European contract) were the project will be continued. These genes could act as tumour suppressors and could have potential applications in clinical oncology (diagnostics, prognostic and therapeutics).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Telomerase, a ribonucleoprotein complex responsible for the maintenance of telomeres, is significantly expressed in 90% of cancer cells and apparently absent in normal somatic cells. Expression of the catalytic protein component of this telomerase complex, hTERT (human Telomerase Reverse Transcriptase), seems to be the limiting factor for telomerase activity, and plays a fundamental role in cellular immortalisation. Moreover, increasing observations indicate that hTERT protein could also have an anti-apoptotic function, independently from its role in telomere elongation.The knowledge of the factors and mechanisms controlling hTERT expression would be highly significant to understand the telomerase re-activation process, a key step during immortalisation and onco-genesis in human cancers. At this date, few transcriptional factors are known to bind hTERT promoter but their actual contribution in telomerase regulation are not demonstrated. Moreover, published data from different laboratories indicate that important relevant transcription factors have not yet been identified.Thus, the factors and mechanisms controlling the hTERT transcription still remain to be elucidated during physiological processes. Using our unique cellular model, in which telomerase can be regulated by several means by a physiological agent, all-trans retinoic acid, we propose to use a cDNA microarray approach to identify and select genes that could be specifically involved in hTERT regulation. In continuation, we will use a functional genomics approach to assess their actual contribution in that process. Our experiments would contribute to a better understanding of hTERT regulation mechanisms, and could also be important for the identification of new target genes for anti-cancer therapy.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY OF BERGEN · BERGENКоординаторНорвегия
Връзки
Данни: CORDIS, © Европейски съюз