title: Regulation of stem cells-related signaling pathways in response to doxorubicin treatment in Hs578T triple-negative breast cancer cells.
abstract: Different molecular changes have been previously associated with therapeutic response and recurrent disease, however, the detailed mechanism of action in triple-negative breast cancer subtype remains elusive. In this study, we investigated the cellular and molecular signaling of two claudin-low triple-negative breast cancer cells to doxorubicin and docetaxel treatment. Whole human transcriptomic evaluation was used to identify the subsequent changes in gene expression, while biological effects were measured by means of proliferation and anchorage-independent growth assays. Microarray analysis revealed changes in stem cell-related signaling pathways, suggesting that doxorubicin treatment affects the balance between self-renewal and differentiation. While the treatment reduced the proliferation, aggregation and mammosphere forming ability of stem-like cells derived from Hs578T cell line, stem-like cells derived from MDA-MB-231 cells were not significantly affected. Our results suggest that claudin-low triple-negative breast cancer cells might predominantly alter stem cell-related signaling pathways to promote stem-like cells activity as an innate resistance mechanism to doxorubicin treatment.
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute I. Chiricuta, Cluj-Napoca, 34-36 Republicii Str, 400015, Cluj-Napoca, Cluj, Romania. oana.tudoran@iocn.ro.|Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Gh. Str., 400337, Cluj-Napoca, Romania. oana.tudoran@iocn.ro.
authors.forename: Oana
authors.initials: O
authors.lastname: Tudoran
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute I. Chiricuta, Cluj-Napoca, 34-36 Republicii Str, 400015, Cluj-Napoca, Cluj, Romania.
authors.forename: Olga
authors.initials: O
authors.lastname: Soritau
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute I. Chiricuta, Cluj-Napoca, 34-36 Republicii Str, 400015, Cluj-Napoca, Cluj, Romania.|Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Gh. Str., 400337, Cluj-Napoca, Romania.
authors.forename: Loredana
authors.initials: L
authors.lastname: Balacescu
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute I. Chiricuta, Cluj-Napoca, 34-36 Republicii Str, 400015, Cluj-Napoca, Cluj, Romania.|Department of Pathologic Anatomy, Necropsy and Veterinary Forensic Medicine, University of Agricultural Sciences and Veterinary Medicine, 3-5 Calea Manastur, 400372, Cluj-Napoca, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Visan
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute I. Chiricuta, Cluj-Napoca, 34-36 Republicii Str, 400015, Cluj-Napoca, Cluj, Romania.
authors.forename: Otilia
authors.initials: O
authors.lastname: Barbos
authors.affiliation: Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Gh. Str., 400337, Cluj-Napoca, Romania.
authors.forename: Roxana
authors.initials: R
authors.lastname: Cojocneanu-Petric
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute I. Chiricuta, Cluj-Napoca, 34-36 Republicii Str, 400015, Cluj-Napoca, Cluj, Romania.
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Balacescu
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute I. Chiricuta, Cluj-Napoca, 34-36 Republicii Str, 400015, Cluj-Napoca, Cluj, Romania.|Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Gh. Str., 400337, Cluj-Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D018874:Spheroids, Cellular / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin
keywords: Breast cancer; Cancer stem-like cells; Chemotherapy; Microarray analysis; Triple negative phenotype