Cisplatin resistance induced in germ cell tumour cells is due to reduced susceptibility towards cell death but not to altered DNA damage induction or repair.
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Cisplatin resistance induced in germ cell tumour cells is due to reduced susceptibility towards cell death but not to altered DNA damage induction or repair. / Fenske, Annabelle E; Glaesener, Stephanie; Bokemeyer, Carsten; Thomale, Juergen; Dahm-Daphi, Jochen; Honecker, Friedemann; Dartsch, Dorothee C.
In: CANCER LETT, Vol. 324, No. 2, 2, 2012, p. 171-178.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cisplatin resistance induced in germ cell tumour cells is due to reduced susceptibility towards cell death but not to altered DNA damage induction or repair.
AU - Fenske, Annabelle E
AU - Glaesener, Stephanie
AU - Bokemeyer, Carsten
AU - Thomale, Juergen
AU - Dahm-Daphi, Jochen
AU - Honecker, Friedemann
AU - Dartsch, Dorothee C
PY - 2012
Y1 - 2012
N2 - To identify factors involved in cisplatin (CDDP) resistance of germ cell tumours (GCTs), we exposed NTERA-2 cells, and the platinum-adapted subline NTERA-2R to CDDP and compared their response. While both cell lines showed comparable proliferation, NTERA-2R cells were clearly more resistant to the drug than the parental NTERA-2 cell line. Interestingly, the two lines showed identical extent of DNA adduct formation and elimination, indicating that neither changes in CDDP uptake, nor altered drug efflux, DNA binding, or repair caused the difference in resistance. Similarly, no difference occurred in the time-course of ?H2AX formation, which was not linked to 53BP1 accumulation. In contrast, NTERA-2R cells showed a more pronounced dose-dependent S phase delay, a transient G(2)/M-block, and subsequent release into immediate cell death. We thus conclude that the enhanced resistance against CDDP is linked to reduced susceptibility to cell death rather than to an altered DNA adduct formation or adduct removal.
AB - To identify factors involved in cisplatin (CDDP) resistance of germ cell tumours (GCTs), we exposed NTERA-2 cells, and the platinum-adapted subline NTERA-2R to CDDP and compared their response. While both cell lines showed comparable proliferation, NTERA-2R cells were clearly more resistant to the drug than the parental NTERA-2 cell line. Interestingly, the two lines showed identical extent of DNA adduct formation and elimination, indicating that neither changes in CDDP uptake, nor altered drug efflux, DNA binding, or repair caused the difference in resistance. Similarly, no difference occurred in the time-course of ?H2AX formation, which was not linked to 53BP1 accumulation. In contrast, NTERA-2R cells showed a more pronounced dose-dependent S phase delay, a transient G(2)/M-block, and subsequent release into immediate cell death. We thus conclude that the enhanced resistance against CDDP is linked to reduced susceptibility to cell death rather than to an altered DNA adduct formation or adduct removal.
KW - Humans
KW - Male
KW - Time Factors
KW - Cell Line, Tumor
KW - Dose-Response Relationship, Drug
KW - Cell Proliferation/drug effects
KW - Cell Survival/drug effects
KW - Drug Resistance, Neoplasm
KW - Cell Death/drug effects
KW - DNA Damage
KW - DNA Repair
KW - Antineoplastic Agents/metabolism/pharmacology
KW - Cell Cycle Checkpoints/drug effects
KW - Cisplatin/metabolism/pharmacology
KW - DNA Adducts/metabolism
KW - Histones/metabolism
KW - Intracellular Signaling Peptides and Proteins/metabolism
KW - Neoplasms, Germ Cell and Embryonal/genetics/pathology
KW - Phosphatidylserines/metabolism
KW - Testicular Neoplasms/genetics/pathology
KW - Humans
KW - Male
KW - Time Factors
KW - Cell Line, Tumor
KW - Dose-Response Relationship, Drug
KW - Cell Proliferation/drug effects
KW - Cell Survival/drug effects
KW - Drug Resistance, Neoplasm
KW - Cell Death/drug effects
KW - DNA Damage
KW - DNA Repair
KW - Antineoplastic Agents/metabolism/pharmacology
KW - Cell Cycle Checkpoints/drug effects
KW - Cisplatin/metabolism/pharmacology
KW - DNA Adducts/metabolism
KW - Histones/metabolism
KW - Intracellular Signaling Peptides and Proteins/metabolism
KW - Neoplasms, Germ Cell and Embryonal/genetics/pathology
KW - Phosphatidylserines/metabolism
KW - Testicular Neoplasms/genetics/pathology
M3 - SCORING: Journal article
VL - 324
SP - 171
EP - 178
JO - CANCER LETT
JF - CANCER LETT
SN - 0304-3835
IS - 2
M1 - 2
ER -
