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Beta-hcg promoter based tumor restrictive gene expression for cancer theraphy

机译:基于β-hcg启动子的肿瘤限制性基因表达用于癌症治疗

摘要

The present invention relates to promoters, enhancers and other regulatory elements that direct expression within tumor cells, comprising nucleotide sequences from the 5′ regulatory region, and transcriptionally active fragments thereof, that control expression of a testicular carcinoma related protein, &bgr;-HCG. Specifically provided are expression vectors, host cells and transgenic animals wherein an &bgr;-HCG regulatory region is capable of controlling expression of a heterologous gene, over-expressing an endogenous gene or an inhibitor of a pathological process or knocking out expression of a specific gene believed to be important in cancer development and/or progression. The invention also relates to methods for using said vectors, cells and animals for screening candidate molecules for agonists and antagonists of cancer development and/or progression. The invention further relates to compositions and methods for modulating expression of compounds within tumor cells, and to screening compounds that modulate expression within tumor cells. Methods for using the molecules and compounds identified by the screening assays for therapeutic treatments also are provided.
机译:本发明涉及指导在肿瘤细胞内表达的启动子,增强子和其他调节元件,包括来自5′-prime的核苷酸序列。调节睾丸癌相关蛋白β-HCG表达的调节区及其转录活性片段。特别提供了表达载体,宿主细胞和转基因动物,其中-HCG调节区能够控制异源基因的表达,过表达内源基因或病理过程的抑制剂或敲除特定基因的表达被认为对癌症的发展和/或进展很重要。本发明还涉及使用所述载体,细胞和动物筛选候选分子的方法,所述候选分子用于癌症发展和/或进展的激动剂和拮抗剂。本发明进一步涉及用于调节肿瘤细胞内化合物表达的组合物和方法,并涉及筛选调节肿瘤细胞内表达的化合物。还提供了使用通过筛选测定法鉴定的分子和化合物进行治疗的方法。

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