Tumour suppressor genes and angiogenesis: the role of TP53 in fibroblasts.
Tumour suppressor genes and angiogenesis: the role of TP53 in fibroblasts.
复制标题
肿瘤抑制基因和血管生成：TP53 在成纤维细胞中的作用。
DOI：
10.1016/s0959-8049(96)00385-1
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Bouck,N
中科院分区：
文献类型：
--
作者：
Stellmach,V;Volpert,OV;Crawford,SE;Lawler,J;Hynes,RO;Bouck,N
As NORMAL cells develop the ability to produce solid tumours, they must acquire at least three key characteristics that differentiate them from their normal progenitors. They must become able to divide easily under conditions where normal cells are either quiescent or dividing in an orderly manner. They must acquire the ability to attract new blood vessels to support their progressive expansion, and they must avoid clearance by the immune system as they undergo these changes. These alterations in phenotype occur as a result of genetic lesions that activate oncogenes and inactivate tumour suppressor genes. There are now more than 50 oncogenes identified. The list of human tumour suppressor genes stands at 16 and is rapidly growing. Thus, there exists an immense number of possible combinations of activated oncogenes and inactive tumour suppressor genes that could, in theory, lead to malignancy. Yet in any single type of human tumour, specific lesions occur in only a restricted subset of oncogenes and tumour suppressor genes. Most colon carcinomas have lost tumour suppressor genes/PC, TP53 and DCC and activated oncogene K-RAS [l]. The majority of pancreatic cancers activate Z&IS and lose the tumour suppressor ZPC [2]. The specific combination of activated oncogenes and inactivated tumour suppressor genes necessary and sufficient to produce a tumour in a given tissue is determined by sequential rounds of clonal selection among the many spontaneously arising mutant clones within the developing tumour [3]. The surprising degree of predictability in a given tissue seems to reflect tissue-specific constraints arising from (i) a limited subset of genetic lesions available for selection to act on, which in turn depends on mutagenic influences specific to that tissue and the sensitivity of the various oncogenes and tumour suppressor genes to such mutagens, and (ii) the strength of the advantage a lesion in a given oncogene or
