Buněčné mechanizmy odpovídající na poškození DNA jako možná bariéra časné nádorové transformace lidských buněk

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F05%3A00027591" target="_blank" >RIV/68378050:_____/05:00027591 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis

Popis výsledku v původním jazyce

In this work we show that proteins which are parts of the DNA damage checkpoints are commonly activated in the early stages of tumourigenesis and that their activation precedes genomic instability and malignant conversion. We found that in the cell culture the checkpoint activation follows increased levels of proteins that deregulate DNA replication as E2F1, cyclin E and CDC25A. Based on our experiments we suggest that the DNA damage response could reflect deregulated DNA replication, since overexpressed cyclin E, CDC25A and E2F1 share the ability to promote unscheduled S-phase entry. As a response to the oncogene overexpression, the checkpoint pathways activate p53 pathway, which leads in the case of severe damage to apoptosis. We presume that the checkpoint pathways prevent or delay tumour progression hence defects of these pathways may allow proliferation, survival, enhanced genomic instability and cancerogenesis.

Název v anglickém jazyce

DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis

Popis výsledku anglicky

In this work we show that proteins which are parts of the DNA damage checkpoints are commonly activated in the early stages of tumourigenesis and that their activation precedes genomic instability and malignant conversion. We found that in the cell culture the checkpoint activation follows increased levels of proteins that deregulate DNA replication as E2F1, cyclin E and CDC25A. Based on our experiments we suggest that the DNA damage response could reflect deregulated DNA replication, since overexpressed cyclin E, CDC25A and E2F1 share the ability to promote unscheduled S-phase entry. As a response to the oncogene overexpression, the checkpoint pathways activate p53 pathway, which leads in the case of severe damage to apoptosis. We presume that the checkpoint pathways prevent or delay tumour progression hence defects of these pathways may allow proliferation, survival, enhanced genomic instability and cancerogenesis.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

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Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2005

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature

ISSN

0028-0836

e-ISSN

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Svazek periodika

434

Číslo periodika v rámci svazku

7035

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

864-870

Kód UT WoS článku

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EID výsledku v databázi Scopus

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