Victorino 2015 Tumour Biol

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Victorino VJ, Barroso WA, Assunção AK, Cury V, Jeremias IC, Petroni R, Chausse B, Ariga SK, Herrera AC, Panis C, Lima TM, Souza HP (2015) PGC-1β regulates HER2-overexpressing breast cancer cells proliferation by metabolic and redox pathways. Tumour Biol 37:6035-44.

» PMID: 26602383

Victorino VJ, Barroso WA, Assuncao AK, Cury V, Jeremias IC, Petroni R, Chausse B, Ariga SK, Herrera AC, Panis C, Lima TM, Souza HP (2015) Tumour Biol

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, Human breast adenocarcinoma SKBR-3 cells

Labels: MiParea: Respiration, Genetic knockout;overexpression, Patients  Pathology: Cancer 

Organism: Human  Tissue;cell: Genital, Other cell lines  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k