Biomarkers and mechanisms of FANCD2 function
Standard
Biomarkers and mechanisms of FANCD2 function. / Willers, Henning; Kachnic, Lisa A; Luo, Chen-Mei; Li, Li; Purschke, Martin; Borgmann, Kerstin; Held, Kathryn D; Powell, Simon N.
in: J BIOMED BIOTECHNOL, Jahrgang 2008, 01.01.2008, S. 821529.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Biomarkers and mechanisms of FANCD2 function
AU - Willers, Henning
AU - Kachnic, Lisa A
AU - Luo, Chen-Mei
AU - Li, Li
AU - Purschke, Martin
AU - Borgmann, Kerstin
AU - Held, Kathryn D
AU - Powell, Simon N
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Genetic or epigenetic inactivation of the pathway formed by the Fanconi anemia (FA) and BRCA1 proteins occurs in several cancer types, making the affected tumors potentially hypersensitive to DNA cross-linkers and other chemotherapeutic agents. It has been proposed that the inability of FA/BRCA-defective cells to form subnuclear foci of effector proteins, such as FANCD2, can be used as a biomarker to aid individualization of chemotherapy. We show that FANCD2 inactivation not only renders cells sensitive to cross-links, but also oxidative stress, a common effect of cancer therapeutics. Oxidative stress sensitivity does not correlate with FANCD2 or RAD51 foci formation, but associates with increased gammaH2AX foci levels and apoptosis. Therefore, FANCD2 may protect cells against cross-links and oxidative stress through distinct mechanisms, consistent with the growing notion that the pathway is not linear. Our data emphasize the need for multiple biomarkers, such as gammaH2AX, FANCD2, and RAD51, to capture all pathway activities.
AB - Genetic or epigenetic inactivation of the pathway formed by the Fanconi anemia (FA) and BRCA1 proteins occurs in several cancer types, making the affected tumors potentially hypersensitive to DNA cross-linkers and other chemotherapeutic agents. It has been proposed that the inability of FA/BRCA-defective cells to form subnuclear foci of effector proteins, such as FANCD2, can be used as a biomarker to aid individualization of chemotherapy. We show that FANCD2 inactivation not only renders cells sensitive to cross-links, but also oxidative stress, a common effect of cancer therapeutics. Oxidative stress sensitivity does not correlate with FANCD2 or RAD51 foci formation, but associates with increased gammaH2AX foci levels and apoptosis. Therefore, FANCD2 may protect cells against cross-links and oxidative stress through distinct mechanisms, consistent with the growing notion that the pathway is not linear. Our data emphasize the need for multiple biomarkers, such as gammaH2AX, FANCD2, and RAD51, to capture all pathway activities.
KW - Biological Markers
KW - Cell Line
KW - Fanconi Anemia
KW - Fanconi Anemia Complementation Group D2 Protein
KW - Fibroblasts
KW - Histones
KW - Humans
KW - Oxidative Stress
KW - Rad51 Recombinase
KW - Signal Transduction
U2 - 10.1155/2008/821529
DO - 10.1155/2008/821529
M3 - SCORING: Journal article
C2 - 18483568
VL - 2008
SP - 821529
ER -