Molecular and Cellular Biochemistry

, Volume 409, Issue 1–2, pp 163–176 | Cite as

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

  • Oana TudoranEmail author
  • Olga Soritau
  • Loredana Balacescu
  • Simona Visan
  • Otilia Barbos
  • Roxana Cojocneanu-Petric
  • Ovidiu Balacescu
  • Ioana Berindan-Neagoe


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.


Triple negative phenotype Breast cancer Cancer stem-like cells Chemotherapy Microarray analysis 



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.

Supplementary material

11010_2015_2522_MOESM1_ESM.pdf (124 kb)
Online resource 1 Microarray top 100 gene expression data of doxorubicin treatment of Hs578T cells (pdf 124 kb)
11010_2015_2522_MOESM2_ESM.pdf (117 kb)
Online resource 2 Microarray gene expression data of docetaxel treatment of Hs578T cells (pdf 116 kb)
11010_2015_2522_MOESM3_ESM.pdf (1 mb)
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)
11010_2015_2522_MOESM4_ESM.pdf (1.4 mb)
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)
11010_2015_2522_MOESM5_ESM.pdf (1.2 mb)
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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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Oana Tudoran
    • 1
    • 2
    Email author
  • Olga Soritau
    • 1
  • Loredana Balacescu
    • 1
    • 2
  • Simona Visan
    • 1
    • 3
  • Otilia Barbos
    • 1
  • Roxana Cojocneanu-Petric
    • 2
  • Ovidiu Balacescu
    • 1
  • Ioana Berindan-Neagoe
    • 1
    • 2
  1. 1.Department of Functional Genomics and Experimental PathologyThe Oncology Institute I. Chiricuta, Cluj-NapocaCluj-NapocaRomania
  2. 2.Research Center for Functional Genomics, Biomedicine and Translational MedicineIuliu Hatieganu University of Medicine and PharmacyCluj-NapocaRomania
  3. 3.Department of Pathologic Anatomy, Necropsy and Veterinary Forensic MedicineUniversity of Agricultural Sciences and Veterinary MedicineCluj-NapocaRomania

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