Tumor Biology

, Volume 37, Issue 5, pp 6035–6044 | Cite as

PGC-1β regulates HER2-overexpressing breast cancer cells proliferation by metabolic and redox pathways

  • Vanessa Jacob Victorino
  • W. A. Barroso
  • A. K. M. Assunção
  • V. Cury
  • I. C. Jeremias
  • R. Petroni
  • B. Chausse
  • S. K. Ariga
  • A. C. S. A. Herrera
  • C. Panis
  • T. M. Lima
  • H. P. Souza
Original Article

Abstract

Breast cancer is a prevalent neoplastic disease among women worldwide which treatments still present several side effects and resistance. Considering that cancer cells present derangements in their energetic homeostasis, and that peroxisome proliferator-activated receptor- gamma coactivator 1 (PGC-1) is crucial for cellular metabolism and redox signaling, the main objective of this study was to investigate whether there is a relationship between PGC-1 expression, the proliferation of breast cancer cells and the mechanisms involved. We initially assessed PGC-1β expression in complementary DNA (cDNA) from breast tumor of patients bearing luminal A, luminal B, and HER2-overexpressed and triple negative tumors. Our data showed that PGC-1β expression is increased in patients bearing HER2-overexpressing tumors as compared to others subtypes. Using quantitative PCR and immunoblotting, we showed that breast cancer cells with HER2-amplification (SKBR-3) have greater expression of PGC-1β as compared to a non-tumorous breast cell (MCF-10A) and higher proliferation rate. PGC-1β expression was knocked down with short interfering RNA in HER2-overexpressing cells, and cells decreased proliferation. In these PGC-1β-inhibited cells, we found increased citrate synthase activity and no marked changes in mitochondrial respiration. Glycolytic pathway was decreased, characterized by lower intracellular lactate levels. In addition, after PGC-1β knockdown, SKBR-3 cells showed increased reactive oxygen species production, no changes in antioxidant activity, and decreased expression of ERRα, a modulator of metabolism. In conclusion, we show an association of HER2-overexpression and PGC-1β. PGC-1β knockdown impairs HER2-overexpressing cells proliferation acting on ERRα signaling, metabolism, and redox balance.

Keywords

Breast cancer subtypes HER2- overexpressing PGC-1β Proliferation 

Notes

Acknowledgments

The authors thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for providing financial support.

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Vanessa Jacob Victorino
    • 1
  • W. A. Barroso
    • 1
  • A. K. M. Assunção
    • 1
  • V. Cury
    • 1
  • I. C. Jeremias
    • 1
  • R. Petroni
    • 1
  • B. Chausse
    • 2
  • S. K. Ariga
    • 1
  • A. C. S. A. Herrera
    • 3
  • C. Panis
    • 4
  • T. M. Lima
    • 1
  • H. P. Souza
    • 1
  1. 1.Laboratório de Investigação Médica – LIM 51, Faculdade de MedicinaUniversidade de São Paulo (FMUSP)São PauloBrazil
  2. 2.Instituto de QuímicaUniversidade de São Paulo (IQ-USP)São PauloBrazil
  3. 3.Faculdade de MedicinaPontifícia Universidade Católica, PUCParanáBrazil
  4. 4.Laboratório de Mediadores InflamatóriosUniversidade Estadual do Oeste do Paraná (UNIOESTE)ParanáBrazil

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