Mechanisms of Action of the p53 Tumor Suppressor and Prospects for Cancer Gene Therapy by Reconstitution of p53 Function
Mechanisms of Action of the p53 Tumor Suppressor and Prospects for Cancer Gene Therapy by Reconstitution of p53 Function
复制标题
p53肿瘤抑制因子的作用机制以及通过重建p53功能进行癌症基因治疗的前景
DOI：
10.1111/j.1749-6632.1994.tb21718.x
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发表时间：
1994
影响因子：
5.2
通讯作者：
T. Friedmann
中科院分区：
文献类型：
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作者：
K. Roemer;T. Friedmann
几十年来，人们已经知道癌症是由基因改变引起的。研究人员已经确定了许多靶基因，当它们突变时，它们有助于肿瘤转化的过程。现在已知突变可以影响用于将细胞外信号转移到细胞核的途径的几乎每个方面。然而，该途径的复杂程度使得难以开发用于治疗癌症的meaninfil治疗方法。然而，在过去的几年中，已经清楚的是，为了成为高度致瘤性，肿瘤细胞通常必须通过“瓶颈”-即，关键的遗传变化，而不管在肿瘤进展过程中在肿瘤细胞中积累的其他几种遗传和表观遗传病变的性质。现在人们了解到，这种瓶颈是由于基因的两个野生型（wt）等位基因（肿瘤抑制基因）失活造成的，这些基因的作用是抑制细胞复制机制。p53肿瘤抑制基因是人类癌症中最常见的已知突变序列，现在认为p53功能对于维持细胞的非致瘤表型是必不可少的。我们和其他人已经提出，通过基因转移和表达恢复肿瘤抑制功能可能是抑制许多不同类型肿瘤的肿瘤表型的有力策略。细胞
It has been known for several decades that cancer is caused by genetic alterations. Researchers have identified numerous target genes that contribute to the process of neoplastic transformation when they become mutated. It is now known that mutations can affect almost every aspect of the pathway used to transfer extracellular signals to the cell nucleus. Yet the degree of complexity of this pathway has made it difficult to develop meaninfil therapeutic approaches to the treatment of cancer. However, in the past few years it has become clear that, in order to become hlly tumorigenic, tumor cells often have to pass through a “bottleneck”-that is, a critical genetic change irrespective of the nature of the several other genetic and epigenetic lesions that accumulate in tumor cells in the course of tumor progression. Such a bottleneck is now understood to result from inactivation of both wild-type (wt) alleles of genes that function as brakes on the mechanisms of cellular replication, the tumor suppressor genes.’J The p53 tumor suppressor gene is the most common known mutated sequence in human cancer^,^ and it is now thought that p53 function is essential for the maintenance of the nontumorigenic phenotype of cells.M For these reasons, we and others have suggested that restoration of tumor suppressor function through gene transfer and expression may be a powerful strategy to suppress the tumor phenotype of many different types of tumor cells.
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M.Ishikawa 等人：Cell Tiss.Res.(1988)
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