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转录与癌症。

Transcription and cancer.

作者信息

Cox P M, Goding C R

机构信息

Transcriptional Control Laboratory, Marie Curie Cancer Research, Oxted, Surrey, UK.

出版信息

Br J Cancer. 1991 May;63(5):651-62. doi: 10.1038/bjc.1991.151.

Abstract

The normal growth, development and function of an organism requires precise and co-ordinated control of gene expression. A major part of this control is exerted by regulating messenger RNA (mRNA) production and involves complex interactions between an array of transcriptionally active proteins and specific regulatory DNA sequences. The combination of such proteins and DNA sequences is specific for given gene or group of genes in a particular cell type and the proteins regulating the same gene may vary between cell types. In addition the expression or activity of these regulatory proteins may be modified depending on the state of differentiation of a cell or in response to an external stimulus. Thus, the differentiation of embryonic cells into diverse tissues is achieved and the mature structure and function of the organism is maintained. This review focusses on the role of perturbations of these transcriptional controls in neoplasia. Deregulation of transcription may result in the failure to express genes responsible for cellular differentiation, or alternatively, in the transcription of genes involved in cell division, through the inappropriate expression or activation of positively acting transcription factors and nuclear oncogenes. Whether the biochemical abnormalities that lead to the disordered growth and differentiation of a malignant tumour affect cell surface receptors, membrane or cytoplasmic signalling proteins or nuclear transcription factors, the end result is the inappropriate expression of some genes and failure to express others. Current research is starting to elucidate which of the elements of this complicated system are important in neoplasia.

摘要

生物体的正常生长、发育和功能需要对基因表达进行精确且协调的控制。这种控制的主要部分是通过调节信使核糖核酸(mRNA)的产生来实现的,并且涉及一系列转录活性蛋白与特定调控DNA序列之间的复杂相互作用。这些蛋白质和DNA序列的组合对于特定细胞类型中的特定基因或基因组是特异的,并且调节同一基因的蛋白质在不同细胞类型之间可能有所不同。此外,这些调控蛋白的表达或活性可能会根据细胞的分化状态或对外部刺激的反应而发生改变。因此,胚胎细胞分化成各种组织得以实现,生物体的成熟结构和功能得以维持。本综述聚焦于这些转录调控紊乱在肿瘤形成中的作用。转录失调可能导致负责细胞分化的基因无法表达,或者通过正性作用转录因子和核癌基因的不适当表达或激活,导致参与细胞分裂的基因转录。无论导致恶性肿瘤生长和分化紊乱的生化异常是影响细胞表面受体、膜或细胞质信号蛋白还是核转录因子,最终结果都是一些基因的不适当表达以及其他一些基因的无法表达。目前的研究开始阐明这个复杂系统中的哪些元件在肿瘤形成中是重要的。

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