Tumor suppressor genes: Possible functions in the negative regulation of cell proliferation
Tumor suppressor genes: Possible functions in the negative regulation of cell proliferation
复制标题
肿瘤抑制基因：负调节细胞增殖的可能功能
作者：
J. Boyd;J. Barrett
癌发生的多步骤模型假定在肿瘤进展过程中发生多种遗传变化。有两类基因，癌基因和肿瘤抑制基因，现在已知在癌症发展中起作用。识别和描述癌基因的任务现在已经进入了第二个十年，至少有两件事是清楚的：存在相对大量的这些基因（保守估计为40-501个，并且它们的激活，主要通过点突变，扩增，或重排，可能会在影响这一过程的复杂生化和分子途径的几乎任何点上产生细胞增殖的阳性信号。相反，肿瘤抑制基因是一类细胞基因，其正常功能是抑制不适当的细胞增殖，并且这些基因在肿瘤细胞中经常丢失、失活或突变。已经克隆了几个与人类癌症相关的真实或推定的肿瘤抑制基因，包括来自视网膜母细胞瘤和其他肿瘤的Rb基因、来自结肠和肺肿瘤的p53基因、来自Wilms肿瘤的WT 1基因、来自结肠肿瘤的DCC基因和来自神经纤维瘤病的Nf-1基因。基因产物的正常功能和机制在很大程度上仍不清楚，尽管有有限的证据表明Rb和WT 1产物作为基因表达的转录调节因子，DCC基因产物与某些细胞粘附分子具有同源性，NF-1基因编码GTP酶激活蛋白。然而，这个基因家族可能参与或控制不同的生长和分化途径。因此，可以提出一系列关于肿瘤抑制基因作用的假设机制。为
Multistep models of carcinogenesis presuppose that multiple genetic changes occur during neoplastic progression. There are two classes of genes, oncogenes and tumor suppressor genes, now known to play a role in cancer development. The task of identification and characterization of oncogenes is now well into its second decade, and at least two matters are clear: a relatively large number of these genes exist (conservative estimates are 40-501, and their activation, primarily through point mutation, amplification, or rearrangement, may result in positive signalling for cell proliferation at virtually any point in the complex biochemical and molecular pathways that affect this process. In contrast, tumor suppressor genes are a class of cellular genes whose normal function is to suppress inappropriate cell proliferation, and the genes are frequently lost, inactivated, or mutated in neoplastic cells. Several ~ O R J fide or putative tumor suppressor genes relevant to human cancers have been cloned [reviewed in 11, including the Rb gene from retinoblastoma and other tumors, the p53gene from colon and lung tumors, the WT1 gene from Wilms‘ tumor, the DCC gene from colon tumors, and the Nf-1 gene from neurofibromatosis. The normal function and mechanism of the gene products remains largely obscure, although there is limited evidence that the Rb and WT1 products act as transcriptional regulators of gene expression, the DCC gene product bears homology to certain cell adhesion molecules, and the NF-I gene encodes a GTPase-activating protein. It is likely, however, that this family of genes is involved in or controls diverse growth and differentiation pathways. A wide range of hypothetical mechanisms by which tumor suppressor genes operate may therefore be proposed. As the
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影响因子：
11.2
作者：
R. Weinberg
通讯作者：
R. Weinberg
影响因子：
56.9
作者：
DYSON, N;HOWLEY, PM;HARLOW, E
通讯作者：
HARLOW, E
DOI：
10.1073/pnas.85.1.121
发表时间：
1988-01-01
影响因子：
11.1
作者：
FEY, EG;PENMAN, S
通讯作者：
PENMAN, S
影响因子：
10.4
作者：
Blum,JL;Zeigler,ME;Wicha,MS
通讯作者：
Wicha,MS