RESUMO
The TRIM family of genes is largely studied because of their roles in development, differentiation and host cell antiviral defenses; however, roles in cancer biology are emerging. Loss of heterozygosity of the TRIM3 locus in â¼20% of human glioblastomas raised the possibility that this NHL-domain containing member of the TRIM gene family might be a mammalian tumor suppressor. Consistent with this, reducing TRIM3 expression increased the incidence of and accelerated the development of platelet-derived growth factor -induced glioma in mice. Furthermore, TRIM3 can bind to the cdk inhibitor p21(WAF1/CIP1). Thus, we conclude that TRIM3 is a tumor suppressor mapping to chromosome 11p15.5 and that it might block tumor growth by sequestering p21 and preventing it from facilitating the accumulation of cyclin D1-cdk4.
Assuntos
Proteínas de Transporte/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Glioblastoma/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Proteínas de Transporte/genética , Linhagem Celular , Linhagem Celular Transformada , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Immunoblotting , Perda de Heterozigosidade , Camundongos , Camundongos Knockout , Mutação , Ligação Proteica , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Supressoras de Tumor/genéticaRESUMO
An array of individually addressable nanoplate field-effect capacitive (bio-)chemical sensors based on an SOI (silicon-on-insulator) structure has been developed. The isolation of the individual capacitors was achieved by forming a trench in the top Si layer with a thickness of 350 nm. The realized sensor array allows addressable biasing and electrical readout of multiple nanoplate EISOI (electrolyte-insulator-silicon-on-insulator) capacitive biosensors on the same SOI chip as well as differential-mode measurements. The feasibility of the proposed approach has been demonstrated by realizing sensors for the pH and penicillin concentration detection as well as for the label-free electrical monitoring of polyelectrolyte multilayers formation and DNA (deoxyribonucleic acid)-hybridization event. A potential change of â¼ 120 mV has been registered after the DNA hybridization for the sensor immobilized with perfectly matched single-strand DNA, while practically no signal changes have been observed for a sensor with fully mismatched DNA. The realized examples demonstrate the potential of the nanoplate SOI capacitors as a new basic structural element for the development of different types of field-effect biosensors.