PGC-1ß regulates HER2-overexpressing breast cancer cells proliferation by metabolic and redox pathways.
Tumour Biol
; 37(5): 6035-44, 2016 May.
Article
in En
| MEDLINE
| ID: mdl-26602383
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-1ß 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-1ß 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-1ß as compared to a non-tumorous breast cell (MCF-10A) and higher proliferation rate. PGC-1ß expression was knocked down with short interfering RNA in HER2-overexpressing cells, and cells decreased proliferation. In these PGC-1ß-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-1ß 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-1ß. PGC-1ß knockdown impairs HER2-overexpressing cells proliferation acting on ERRα signaling, metabolism, and redox balance.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidation-Reduction
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Breast Neoplasms
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Carrier Proteins
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Gene Expression Regulation, Neoplastic
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Genes, erbB-2
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Metabolic Networks and Pathways
Limits:
Aged
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Female
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Humans
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Middle aged
Language:
En
Journal:
Tumour Biol
Journal subject:
NEOPLASIAS
Year:
2016
Document type:
Article
Affiliation country: