Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer.
Nat Commun
; 4: 2175, 2013.
Article
em En
| MEDLINE
| ID: mdl-23868472
ABSTRACT
About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Receptores do Ácido Retinoico
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Resistencia a Medicamentos Antineoplásicos
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Receptor alfa de Estrogênio
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Recidiva Local de Neoplasia
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2013
Tipo de documento:
Article