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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. / Bartkova, Jirina; Horejsí, Zuzana; Koed, Karen; Krämer, Alwin; Tort, Frederic; Zieger, Karsten; Guldberg, Per; Sehested, Maxwell; Nesland, Jahn M; Lukas, Claudia; Ørntoft, Torben; Lukas, Jiri; Bartek, Jiri.

In: Nature, Vol. 434, No. 7035, 14.04.2005, p. 864-70.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bartkova, J, Horejsí, Z, Koed, K, Krämer, A, Tort, F, Zieger, K, Guldberg, P, Sehested, M, Nesland, JM, Lukas, C, Ørntoft, T, Lukas, J & Bartek, J 2005, 'DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis', Nature, vol. 434, no. 7035, pp. 864-70. https://doi.org/10.1038/nature03482

APA

Bartkova, J., Horejsí, Z., Koed, K., Krämer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J. M., Lukas, C., Ørntoft, T., Lukas, J., & Bartek, J. (2005). DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature, 434(7035), 864-70. https://doi.org/10.1038/nature03482

Vancouver

Bartkova J, Horejsí Z, Koed K, Krämer A, Tort F, Zieger K et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005 Apr 14;434(7035):864-70. https://doi.org/10.1038/nature03482

Author

Bartkova, Jirina ; Horejsí, Zuzana ; Koed, Karen ; Krämer, Alwin ; Tort, Frederic ; Zieger, Karsten ; Guldberg, Per ; Sehested, Maxwell ; Nesland, Jahn M ; Lukas, Claudia ; Ørntoft, Torben ; Lukas, Jiri ; Bartek, Jiri. / DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. In: Nature. 2005 ; Vol. 434, No. 7035. pp. 864-70.

Bibtex

@article{0e454ad14c144f678d60192386f5b6fd,
title = "DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis",
abstract = "During the evolution of cancer, the incipient tumour experiences 'oncogenic stress', which evokes a counter-response to eliminate such hazardous cells. However, the nature of this stress remains elusive, as does the inducible anti-cancer barrier that elicits growth arrest or cell death. Here we show that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions (but not normal tissues) commonly express markers of an activated DNA damage response. These include phosphorylated kinases ATM and Chk2, and phosphorylated histone H2AX and p53. Similar checkpoint responses were induced in cultured cells upon expression of different oncogenes that deregulate DNA replication. Together with genetic analyses, including a genome-wide assessment of allelic imbalances, our data indicate that early in tumorigenesis (before genomic instability and malignant conversion), human cells activate an ATR/ATM-regulated DNA damage response network that delays or prevents cancer. Mutations compromising this checkpoint, including defects in the ATM-Chk2-p53 pathway, might allow cell proliferation, survival, increased genomic instability and tumour progression.",
keywords = "Allelic Imbalance/genetics, Cell Cycle, Cell Cycle Proteins/genetics, Cell Line, Tumor, Cell Transformation, Neoplastic/genetics, Checkpoint Kinase 2, Cyclin E/genetics, DNA Damage/genetics, DNA-Binding Proteins/genetics, E2F Transcription Factors, Enzyme Activation, Genes, p53/genetics, Genomic Instability, Humans, Mutation/genetics, Neoplasms/enzymology, Oncogenes/genetics, Phosphorylation, Polymorphism, Single Nucleotide/genetics, Protein-Serine-Threonine Kinases/metabolism, Signal Transduction, Transcription Factors/genetics, Urinary Bladder Neoplasms/enzymology, cdc25 Phosphatases/genetics",
author = "Jirina Bartkova and Zuzana Horejs{\'i} and Karen Koed and Alwin Kr{\"a}mer and Frederic Tort and Karsten Zieger and Per Guldberg and Maxwell Sehested and Nesland, {Jahn M} and Claudia Lukas and Torben {\O}rntoft and Jiri Lukas and Jiri Bartek",
year = "2005",
month = apr,
day = "14",
doi = "10.1038/nature03482",
language = "English",
volume = "434",
pages = "864--70",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7035",

}

RIS

TY - JOUR

T1 - DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis

AU - Bartkova, Jirina

AU - Horejsí, Zuzana

AU - Koed, Karen

AU - Krämer, Alwin

AU - Tort, Frederic

AU - Zieger, Karsten

AU - Guldberg, Per

AU - Sehested, Maxwell

AU - Nesland, Jahn M

AU - Lukas, Claudia

AU - Ørntoft, Torben

AU - Lukas, Jiri

AU - Bartek, Jiri

PY - 2005/4/14

Y1 - 2005/4/14

N2 - During the evolution of cancer, the incipient tumour experiences 'oncogenic stress', which evokes a counter-response to eliminate such hazardous cells. However, the nature of this stress remains elusive, as does the inducible anti-cancer barrier that elicits growth arrest or cell death. Here we show that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions (but not normal tissues) commonly express markers of an activated DNA damage response. These include phosphorylated kinases ATM and Chk2, and phosphorylated histone H2AX and p53. Similar checkpoint responses were induced in cultured cells upon expression of different oncogenes that deregulate DNA replication. Together with genetic analyses, including a genome-wide assessment of allelic imbalances, our data indicate that early in tumorigenesis (before genomic instability and malignant conversion), human cells activate an ATR/ATM-regulated DNA damage response network that delays or prevents cancer. Mutations compromising this checkpoint, including defects in the ATM-Chk2-p53 pathway, might allow cell proliferation, survival, increased genomic instability and tumour progression.

AB - During the evolution of cancer, the incipient tumour experiences 'oncogenic stress', which evokes a counter-response to eliminate such hazardous cells. However, the nature of this stress remains elusive, as does the inducible anti-cancer barrier that elicits growth arrest or cell death. Here we show that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions (but not normal tissues) commonly express markers of an activated DNA damage response. These include phosphorylated kinases ATM and Chk2, and phosphorylated histone H2AX and p53. Similar checkpoint responses were induced in cultured cells upon expression of different oncogenes that deregulate DNA replication. Together with genetic analyses, including a genome-wide assessment of allelic imbalances, our data indicate that early in tumorigenesis (before genomic instability and malignant conversion), human cells activate an ATR/ATM-regulated DNA damage response network that delays or prevents cancer. Mutations compromising this checkpoint, including defects in the ATM-Chk2-p53 pathway, might allow cell proliferation, survival, increased genomic instability and tumour progression.

KW - Allelic Imbalance/genetics

KW - Cell Cycle

KW - Cell Cycle Proteins/genetics

KW - Cell Line, Tumor

KW - Cell Transformation, Neoplastic/genetics

KW - Checkpoint Kinase 2

KW - Cyclin E/genetics

KW - DNA Damage/genetics

KW - DNA-Binding Proteins/genetics

KW - E2F Transcription Factors

KW - Enzyme Activation

KW - Genes, p53/genetics

KW - Genomic Instability

KW - Humans

KW - Mutation/genetics

KW - Neoplasms/enzymology

KW - Oncogenes/genetics

KW - Phosphorylation

KW - Polymorphism, Single Nucleotide/genetics

KW - Protein-Serine-Threonine Kinases/metabolism

KW - Signal Transduction

KW - Transcription Factors/genetics

KW - Urinary Bladder Neoplasms/enzymology

KW - cdc25 Phosphatases/genetics

U2 - 10.1038/nature03482

DO - 10.1038/nature03482

M3 - Journal article

C2 - 15829956

VL - 434

SP - 864

EP - 870

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7035

ER -

ID: 246727912