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Eur Arch Otorhinolaryngol ; 261(4): 208-15, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12915945

RESUMO

The aim of gene therapy includes the tight spatial and temporal control of transgenic expression. There are several approaches concerning externally inducible gene promoters used for the control of suicide genes. Two of the promoters that might play a role in head and neck cancer gene therapy are the hyperthermia-inducible human heat shock protein-70 (hsp70) promotor, as well as the radiation-inducible promoter of the early growth response-1 gene (egr-1). We tested the hsp-70 promoter as well as a promoter construct, containing synthetic radio-responsive elements of the egr-1 enhancer for the effect on reporter gene expression in two stably transfected head and neck carcinoma cell lines in vitro and measured the success of gene activation by FACS analysis, western blot analysis and fluorescence microscopy. With the hsp70 promoter we reached a 5.83-fold increase of reporter gene expression after hyperthermic treatment in one of the two cell lines tested. The radiation-inducible construct revealed only weak gene induction and was marked by high background expression. Both systems worked in a highly cell-type dependent manner. The possible clinical use of externally inducible transgene expression in head and neck carcinoma gene therapy is critically discussed.


Assuntos
Técnicas de Transferência de Genes , Proteínas de Choque Térmico HSP70/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Regiões Promotoras Genéticas , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Regulação da Expressão Gênica , Genes Reporter , Neoplasias de Cabeça e Pescoço/genética , Humanos , Hipertermia Induzida , Técnicas In Vitro , Microscopia de Fluorescência , Valores de Referência , Sensibilidade e Especificidade , Ativação Transcricional , Transfecção , Células Tumorais Cultivadas
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