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Regulation of stem cells-related signaling pathways in response to doxorubicin treatment in Hs578T triple-negative breast cancer cells

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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.

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Acknowledgments

This work was financed by the POSCCE 709/2010 grant with the title: “Clinical and economical impact of proteome and transcriptome molecular profiling in neoadjuvant therapy of triple negative breast cancer (BREASTIMPACT)”, and published under the frame of European Social Fund, Human Resources Development Operational Programme 2007–2013, Project No. POSDRU/159/1.5/S/138776.

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Authors and Affiliations

  1. 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, Olga Soritau, Loredana Balacescu, Simona Visan, Otilia Barbos, Ovidiu Balacescu & Ioana Berindan-Neagoe

  2. 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, Loredana Balacescu, Roxana Cojocneanu-Petric & Ioana Berindan-Neagoe

  3. Department of Pathologic Anatomy, Necropsy and Veterinary Forensic Medicine, University of Agricultural Sciences and Veterinary Medicine, 3-5 Calea Manastur, 400372, Cluj-Napoca, Romania

    Simona Visan

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  1. Oana Tudoran
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Electronic supplementary material

Below is the link to the electronic supplementary material.

Online resource 1

Microarray top 100 gene expression data of doxorubicin treatment of Hs578T cells (pdf 124 kb)

Online resource 2

Microarray gene expression data of docetaxel treatment of Hs578T cells (pdf 116 kb)

Online resource 3

Regulation of “Mouse embryonic stem cells pluripotency” signaling pathway in response to doxorubicin treatment of Hs578T cells. Genes highlighted in red were found to be up-regulated by doxorubicin treatment, while the genes highlighted in green were down-regulated (pdf 1064 kb)

Online resource 4

Regulation of “Role of OCT4 in Mammalian Embryonic Stem Cell Pluripotency” signaling pathway in response to doxorubicin treatment of Hs578T cells. Genes highlighted in red were found to be up-regulated by doxorubicin treatment, while the genes highlighted in green were down-regulated (pdf 1448 kb)

Online resource 5

Regulation of “Role of Nanog in Mammalian Embryonic Stem Cell Pluripotency” signaling pathway in response to doxorubicin treatment of Hs578T cells. Genes highlighted in red were found to be up-regulated by doxorubicin treatment, while the genes highlighted in green were down-regulated (pdf 1260 kb)

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Tudoran, O., Soritau, O., Balacescu, L. et al. Regulation of stem cells-related signaling pathways in response to doxorubicin treatment in Hs578T triple-negative breast cancer cells. Mol Cell Biochem 409, 163–176 (2015). https://doi.org/10.1007/s11010-015-2522-z

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