title: Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line.
abstract: Triple-negative breast cancers (TNBCs) are defined as tumors that lack expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Clinically, TNBC patients are treated with cytotoxic drugs including 5-fluorouracil (5-FU). However, TNBCs develop resistance to such drugs after a series of treatments. To elucidate the mechanisms of drug resistance, establishment of drug-resistant cancer cell lines should be one of the most useful model systems. However, 5-FU-resistant TNBC cell lines have not been previously reported. In this study, we established a 5-FU-resistant cell line, MDA-MB-231/5-FU, from the human TNBC cell line MDA-MB-231, by repeated exposure to stepwise increases in the concentration of 5-FU. The IC₅₀ value of 5-FU for MDA-MB-231/5-FU was 5.5-fold that for the parental cells. The MDA-MB-231/5-FU cell line acquired resistance to not only 5-FU, but also vinorelbine, paclitaxel and gemcitabine. Additionally, we performed iTRAQ-based quantitative proteomics in MDA-MB-231/5-FU cells and the parental cells in order to characterize MDA-MB-231/5-FU. The proteins upregulated in the newly established cells were mainly classified into the categories of 'DNA recombination', 'cell cycle', 'complex assembly', 'cytoskeleton organization', 'transport' and 'negative regulation of cell death'. These proteins may be related to mechanisms of drug resistance in TNBCs. Our established MDA-MB-231/5-FU cell line should be a useful tool for identifying new mechanisms of drug resistance and new drug targets in TNBCs.
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masako
authors.initials: M
authors.lastname: Tanaka
authors.forename: Azusa
authors.initials: A
authors.lastname: Inagaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nagayama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D020543:Proteome / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005472:Fluorouracil; D017239:Paclitaxel; D020543:Proteome; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; C508053:ERBB2 protein, human