RESUMO
Breast cancer stem cells are defined as cancer cells with self-renewal capacity. These cells represent a small subpopulation endowed with the ability to form new tumours when injected in nude mice. Markers of differentiation have been used to identify these cancer cells. In the case of breast cancer, CD44+/CD24- select a population with stem cell properties. The fact that these cells have self-renewal ability has suggested that this population could be responsible for new tumour formation and cancer relapse. These cells have been shown to be more resistant to chemotherapy and radiotherapy than normal cancer cells. The identification of the molecular druggable alterations responsible for the initiation and maintenance of cancer stem cells is an important goal. In this article we will review all these points with special emphasis on the possible role of new drugs designed to interact with molecular pathways of cancer stem cells (AU)
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Assuntos
Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Biomarcadores Tumorais/genética , Células-Tronco Neoplásicas/patologia , Sistemas de Liberação de Medicamentos/métodos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Diferenciação Celular/genética , Desenho de Fármacos , Meio Ambiente , Modelos Biológicos , Células-Tronco Neoplásicas/metabolismo , Biomarcadores Tumorais/metabolismoRESUMO
El gen mutado en el síndrome de Ataxia Telangiectasia está implicado en múltiples funciones celulares queabarcan desde la respuesta al daño genotóxico causado por la radiación ionizante hasta la respuesta a insulina.Curiosamente la ruta de señalización mediada por Akt esta relacionada con los mismos estímulos. En el presenteestudio demostramos como el gen mutado en Ataxia Telangiectasia (ATM) controla la fosforilación deAkt, en respuesta a estímulos como la radiación ionizante o la insulina. Estos datos han sido obtenidos usandomodelos experimentales como células derivadas de enfermos de Ataxia o de ratones nulos para la expresión deATM. Nuestro estudio propone nuevas explicaciones para entender la radio sensibilidad característica de estosenfermos y destaca el papel primordial de Akt en la respuesta a la radiación ionizante
The gene mutated in ataxia telangiectasia (ATM) has been implicated in several functions such as cell cycle, response to DNA damage, and insulin. Curiously, the PKB/Akt-mediated signaling route is related to the same cellular responses. We show in this work that ATM is a major determinant of full PKB/Akt activation in response to insulin or gamma-radiation. This conclusion was inferred from the results obtained in transient transfection assays using exogenous PKB/Akt and ATM in Cos cells, and also in cell lines derived from ataxia telangiectasia patients or KO mice. Our study proposes new clues to understand the radiosensitivity associated to ataxia telangiectasia and supports a critical role for PKB/Akt in the cellular response to ionizing radiation
