RESUMO
Emerging studies support that the polycomb repressive complex 2 (PRC2) regulates phenotypic changes of carcinoma cells by modulating their shifts among metastable states within the epithelial and mesenchymal spectrum. This new role of PRC2 in cancer has been recently proposed to stem from the ability of its catalytic subunit EZH2 to bind and modulate the transcription of mesenchymal genes during epithelial-mesenchymal transition (EMT) in lung cancer cells. Here, we asked whether this mechanism is conserved in other types of carcinomas. By combining TGF-ß-mediated reversible induction of epithelial to mesenchymal transition and inhibition of EZH2 methyltransferase activity, we demonstrate that EZH2 represses a large set of mesenchymal genes and favours the residence of breast cancer cells towards the more epithelial spectrum during EMT. In agreement, analysis of human patient samples supports that EZH2 is required to efficiently repress mesenchymal genes in breast cancer tumours. Our results indicate that PRC2 operates through similar mechanisms in breast and lung cancer cells. We propose that PRC2-mediated direct transcriptional modulation of the mesenchymal gene expression programme is a conserved molecular mechanism underlying cell dissemination across human carcinomas.
Assuntos
Neoplasias da Mama , Proteína Potenciadora do Homólogo 2 de Zeste , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Linhagem Celular Tumoral , Fator de Crescimento Transformador beta/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Complexo Repressor Polycomb 2/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismoRESUMO
OBJECTIVE: The aim of this article is to perform a narrative review of how pharmacogenetics and pharmacogenomics is being applied in the clinic, especially in Spain. METHOD: Publications and websites of major interest have been reviewed. RESULTS: Pharmacogenes and variants used in several hospitals, available methodologies, and the implementation process are discussed.
Assuntos
Farmacogenética , Medicina de Precisão , Humanos , EspanhaRESUMO
OBJECTIVE: The aim of this article was to perform a narrative review of how pharmacogenetics and pharmacogenomics is being applied in the clinics, especially in Spain. METHOD: Publications and websites of major interest have been reviewed. RESULTS: Pharmacogenes and variants used in several hospitals, available methodologies, and the implementation process are discussed.
Assuntos
Farmacogenética , Medicina de Precisão , Humanos , EspanhaRESUMO
La diabetes es una enfermedad de alta prevalencia cuyo tratamiento y control reduce la morbilidad y prolonga la supervivencia. El farmacéutico puede y debe jugar un papel importante en el seguimiento farmacoterapéutico de los pacientes diabéticos con el objetivo de detectar y resolver problemas relacionados con medicamentos (PRM). En este artículo se revisan los aspectos clave del tratamiento y control, haciendo énfasis en los indicadores analíticos a fin de poder informar y ayudar a la toma de decisiones (AU)
No disponible
Assuntos
Humanos , Diabetes Mellitus/tratamento farmacológico , Assistência ao Paciente , Assistência Farmacêutica , Hipoglicemiantes/uso terapêutico , Seguimentos , Tomada de Decisões , Hipoglicemiantes/efeitos adversosRESUMO
No disponible
Assuntos
Humanos , Faculdades de Farmácia , Educação em Farmácia/métodos , Educação de Pós-Graduação em Farmácia , EspanhaRESUMO
No disponible