Victorino 2015 Tumour Biol: Difference between revisions
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Revision as of 11:18, 8 November 2016
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. |
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-1Ξ² 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-1Ξ² 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-1Ξ² as compared to a non-tumorous breast cell (MCF-10A) and higher proliferation rate. PGC-1Ξ² expression was knocked down with short interfering RNA in HER2-overexpressing cells, and cells decreased proliferation. In these PGC-1Ξ²-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-1Ξ² knockdown, SKBR-3 cells showed increased reactive oxygen species production, no changes in antioxidant activity, and decreased expression of ERRΞ±, a modulator of metabolism. In conclusion, we show an association of HER2-overexpression and PGC-1Ξ². PGC-1Ξ² knockdown impairs HER2-overexpressing cells proliferation acting on ERRΞ± signaling, metabolism, and redox balance. β’ Keywords: Breast cancer subtypes, HER2-overexpressing, PGC-1Ξ², Proliferation, Human breast adenocarcinoma SKBR-3 cells
Labels: MiParea: Respiration, Genetic knockout;overexpression, Patients
Pathology: Cancer
Organism: Human Tissue;cell: Genital Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
Pathway: ROX
HRR: Oxygraph-2k
2016-01