Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

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Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. / Jandu, Haatisha; Aluzaité, Kristina; Fogh, Louise; Thrane, Sebastian Wingaard; Noer, Julie B; Proszek, Joanna; Nguyen Do, Khoa; Hansen, Stine Ninel; Damsgaard-Hansen, Britt; Nielsen, Signe Lykke; Stougaard, Magnus; Knudsen, Birgitta R.; Moreira, José; Hamerlik, Petra; Gajjar, Madhavsai; Smid, Marcel; Martens, John; Foekens, John; Pommier, Yves; Brünner, Nils; Rasmussen, Anne-Sofie Schrohl; Stenvang, Jan.

In: B M C Cancer, Vol. 16, 34, 22.01.2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jandu, H, Aluzaité, K, Fogh, L, Thrane, SW, Noer, JB, Proszek, J, Nguyen Do, K, Hansen, SN, Damsgaard-Hansen, B, Nielsen, SL, Stougaard, M, Knudsen, BR, Moreira, J, Hamerlik, P, Gajjar, M, Smid, M, Martens, J, Foekens, J, Pommier, Y, Brünner, N, Rasmussen, A-SS & Stenvang, J 2016, 'Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines' B M C Cancer, vol. 16, 34. https://doi.org/10.1186/s12885-016-2071-1

APA

Jandu, H., Aluzaité, K., Fogh, L., Thrane, S. W., Noer, J. B., Proszek, J., ... Stenvang, J. (2016). Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. B M C Cancer, 16, [34]. https://doi.org/10.1186/s12885-016-2071-1

Vancouver

Jandu H, Aluzaité K, Fogh L, Thrane SW, Noer JB, Proszek J et al. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. B M C Cancer. 2016 Jan 22;16. 34. https://doi.org/10.1186/s12885-016-2071-1

Author

Jandu, Haatisha ; Aluzaité, Kristina ; Fogh, Louise ; Thrane, Sebastian Wingaard ; Noer, Julie B ; Proszek, Joanna ; Nguyen Do, Khoa ; Hansen, Stine Ninel ; Damsgaard-Hansen, Britt ; Nielsen, Signe Lykke ; Stougaard, Magnus ; Knudsen, Birgitta R. ; Moreira, José ; Hamerlik, Petra ; Gajjar, Madhavsai ; Smid, Marcel ; Martens, John ; Foekens, John ; Pommier, Yves ; Brünner, Nils ; Rasmussen, Anne-Sofie Schrohl ; Stenvang, Jan. / Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. In: B M C Cancer. 2016 ; Vol. 16.

Bibtex

@article{150736c857114343a8f01d9fb328006c,
title = "Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines",
abstract = "BACKGROUND: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 {\%} response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC.METHODS: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6 months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump.RESULTS: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance.CONCLUSIONS: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan.",
keywords = "Faculty of Social Sciences, Breast cancer, Topoisomerase I, Irinotecan, SN-38, Resistance, ABCG2/BCRP",
author = "Haatisha Jandu and Kristina Aluzait{\'e} and Louise Fogh and Thrane, {Sebastian Wingaard} and Noer, {Julie B} and Joanna Proszek and {Nguyen Do}, Khoa and Hansen, {Stine Ninel} and Britt Damsgaard-Hansen and Nielsen, {Signe Lykke} and Magnus Stougaard and Knudsen, {Birgitta R.} and Jos{\'e} Moreira and Petra Hamerlik and Madhavsai Gajjar and Marcel Smid and John Martens and John Foekens and Yves Pommier and Nils Br{\"u}nner and Rasmussen, {Anne-Sofie Schrohl} and Jan Stenvang",
year = "2016",
month = "1",
day = "22",
doi = "10.1186/s12885-016-2071-1",
language = "English",
volume = "16",
journal = "B M C Cancer",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

AU - Jandu, Haatisha

AU - Aluzaité, Kristina

AU - Fogh, Louise

AU - Thrane, Sebastian Wingaard

AU - Noer, Julie B

AU - Proszek, Joanna

AU - Nguyen Do, Khoa

AU - Hansen, Stine Ninel

AU - Damsgaard-Hansen, Britt

AU - Nielsen, Signe Lykke

AU - Stougaard, Magnus

AU - Knudsen, Birgitta R.

AU - Moreira, José

AU - Hamerlik, Petra

AU - Gajjar, Madhavsai

AU - Smid, Marcel

AU - Martens, John

AU - Foekens, John

AU - Pommier, Yves

AU - Brünner, Nils

AU - Rasmussen, Anne-Sofie Schrohl

AU - Stenvang, Jan

PY - 2016/1/22

Y1 - 2016/1/22

N2 - BACKGROUND: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC.METHODS: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6 months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump.RESULTS: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance.CONCLUSIONS: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan.

AB - BACKGROUND: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC.METHODS: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6 months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump.RESULTS: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance.CONCLUSIONS: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan.

KW - Faculty of Social Sciences

KW - Breast cancer

KW - Topoisomerase I

KW - Irinotecan

KW - SN-38

KW - Resistance

KW - ABCG2/BCRP

U2 - 10.1186/s12885-016-2071-1

DO - 10.1186/s12885-016-2071-1

M3 - Journal article

VL - 16

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

M1 - 34

ER -

ID: 160449210