Research ExplorerPublicationsCyclosporin A, but not everolimus, inhibits DNA repair media...

Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression

Standard

Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression. / Thoms, Kai-Martin; Kuschal, Christiane; Oetjen, Elke; Mori, Toshio; Kobayashi, Nobuhiko; Laspe, Petra; Boeckmann, Lars; Schön, Michael P; Emmert, Steffen.

In: EXP DERMATOL, Vol. 20, No. 3, 03.2011, p. 232-6.

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

Harvard

Thoms, K-M, Kuschal, C, Oetjen, E, Mori, T, Kobayashi, N, Laspe, P, Boeckmann, L, Schön, MP & Emmert, S 2011, 'Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression', EXP DERMATOL, vol. 20, no. 3, pp. 232-6. https://doi.org/10.1111/j.1600-0625.2010.01213.x

APA

Thoms, K-M., Kuschal, C., Oetjen, E., Mori, T., Kobayashi, N., Laspe, P., Boeckmann, L., Schön, M. P., & Emmert, S. (2011). Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression. EXP DERMATOL, 20(3), 232-6. https://doi.org/10.1111/j.1600-0625.2010.01213.x

Vancouver

Thoms K-M, Kuschal C, Oetjen E, Mori T, Kobayashi N, Laspe P et al. Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression. EXP DERMATOL. 2011 Mar;20(3):232-6. https://doi.org/10.1111/j.1600-0625.2010.01213.x

Bibtex

@article{96e27d10e73e48d584bbb2239f028348,
title = "Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression",
abstract = "Unlike other immunosuppressive drugs including everolimus, cyclosporin A causes a dramatic increase of UV-induced skin cancer, a feature that is reminiscent of xeroderma pigmentosum (XP), where defective nucleotide excision repair (NER) of UV-induced DNA damage results in cutaneous carcinogenesis. The molecular basis of the clinically important differential activities of cyclosporin A and everolimus is still unclear. We measured post-UV cell survival of cyclosporin A- and everolimus-treated human fibroblasts and lymphoblasts using a cell proliferation assay (MTT). The cellular NER capacity was assessed by host cell reactivation. Using an ELISA and specific antibodies, cyclobutane pyrimidine and pyrimidine-6,4-pyrimidone photoproduct removal from the cellular genome was measured. The effect of calcineurin on NER was investigated using a calcineurin A expression vector and specific RNAi. Cyclosporin A led to a dose dependent decrease in post-UV cell survival, inhibited NER and blocked photoproduct removal. In contrast, none of these effects where seen in everolimus-treated cells. Overexpression of calcineurin A resulted in increased NER and complemented the Cyclosporin A-induced reduction of NER. Downregulation of calcineurin using RNAi inhibited NER comparable to cyclosporin A-treatment. We conclude that cyclosporin A, but not everolimus, leads to an increased skin cancer risk via a calcineurin signalling-dependent impairment of NER.",
keywords = "Calcineurin, Cell Line, Transformed, Cell Survival, Cyclosporine, DNA Repair, Fibroblasts, Humans, Immunosuppression, Immunosuppressive Agents, Lymphocytes, Neoplasms, Phosphorylation, Pyrimidine Dimers, RNA, Small Interfering, Ribosomal Protein S6 Kinases, 70-kDa, Sirolimus, Transfection, Ultraviolet Rays",
author = "Kai-Martin Thoms and Christiane Kuschal and Elke Oetjen and Toshio Mori and Nobuhiko Kobayashi and Petra Laspe and Lars Boeckmann and Sch{\"o}n, {Michael P} and Steffen Emmert",
note = "{\textcopyright} 2010 John Wiley & Sons A/S.",
year = "2011",
month = mar,
doi = "10.1111/j.1600-0625.2010.01213.x",
language = "English",
volume = "20",
pages = "232--6",
journal = "EXP DERMATOL",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression

AU - Thoms, Kai-Martin

AU - Kuschal, Christiane

AU - Oetjen, Elke

AU - Mori, Toshio

AU - Kobayashi, Nobuhiko

AU - Laspe, Petra

AU - Boeckmann, Lars

AU - Schön, Michael P

AU - Emmert, Steffen

N1 - © 2010 John Wiley & Sons A/S.

PY - 2011/3

Y1 - 2011/3

N2 - Unlike other immunosuppressive drugs including everolimus, cyclosporin A causes a dramatic increase of UV-induced skin cancer, a feature that is reminiscent of xeroderma pigmentosum (XP), where defective nucleotide excision repair (NER) of UV-induced DNA damage results in cutaneous carcinogenesis. The molecular basis of the clinically important differential activities of cyclosporin A and everolimus is still unclear. We measured post-UV cell survival of cyclosporin A- and everolimus-treated human fibroblasts and lymphoblasts using a cell proliferation assay (MTT). The cellular NER capacity was assessed by host cell reactivation. Using an ELISA and specific antibodies, cyclobutane pyrimidine and pyrimidine-6,4-pyrimidone photoproduct removal from the cellular genome was measured. The effect of calcineurin on NER was investigated using a calcineurin A expression vector and specific RNAi. Cyclosporin A led to a dose dependent decrease in post-UV cell survival, inhibited NER and blocked photoproduct removal. In contrast, none of these effects where seen in everolimus-treated cells. Overexpression of calcineurin A resulted in increased NER and complemented the Cyclosporin A-induced reduction of NER. Downregulation of calcineurin using RNAi inhibited NER comparable to cyclosporin A-treatment. We conclude that cyclosporin A, but not everolimus, leads to an increased skin cancer risk via a calcineurin signalling-dependent impairment of NER.

AB - Unlike other immunosuppressive drugs including everolimus, cyclosporin A causes a dramatic increase of UV-induced skin cancer, a feature that is reminiscent of xeroderma pigmentosum (XP), where defective nucleotide excision repair (NER) of UV-induced DNA damage results in cutaneous carcinogenesis. The molecular basis of the clinically important differential activities of cyclosporin A and everolimus is still unclear. We measured post-UV cell survival of cyclosporin A- and everolimus-treated human fibroblasts and lymphoblasts using a cell proliferation assay (MTT). The cellular NER capacity was assessed by host cell reactivation. Using an ELISA and specific antibodies, cyclobutane pyrimidine and pyrimidine-6,4-pyrimidone photoproduct removal from the cellular genome was measured. The effect of calcineurin on NER was investigated using a calcineurin A expression vector and specific RNAi. Cyclosporin A led to a dose dependent decrease in post-UV cell survival, inhibited NER and blocked photoproduct removal. In contrast, none of these effects where seen in everolimus-treated cells. Overexpression of calcineurin A resulted in increased NER and complemented the Cyclosporin A-induced reduction of NER. Downregulation of calcineurin using RNAi inhibited NER comparable to cyclosporin A-treatment. We conclude that cyclosporin A, but not everolimus, leads to an increased skin cancer risk via a calcineurin signalling-dependent impairment of NER.

KW - Calcineurin

KW - Cell Line, Transformed

KW - Cell Survival

KW - Cyclosporine

KW - DNA Repair

KW - Fibroblasts

KW - Humans

KW - Immunosuppression

KW - Immunosuppressive Agents

KW - Lymphocytes

KW - Neoplasms

KW - Phosphorylation

KW - Pyrimidine Dimers

KW - RNA, Small Interfering

KW - Ribosomal Protein S6 Kinases, 70-kDa

KW - Sirolimus

KW - Transfection

KW - Ultraviolet Rays

U2 - 10.1111/j.1600-0625.2010.01213.x

DO - 10.1111/j.1600-0625.2010.01213.x

M3 - SCORING: Journal article

C2 - 21323745

VL - 20

SP - 232

EP - 236

JO - EXP DERMATOL

JF - EXP DERMATOL

SN - 0906-6705

IS - 3

ER -