Eeles R A, Bartkova J, Lane D P, Bartek J
Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey.
Cancer Surv. 1993;18:57-75.
The TP53 protein is proving to be central to cell cycle control after exposure to DNA damage, and every week a new feature of its role in the regulation of cell division is described. TP53 is the most commonly altered oncogene in human tumours and is involved in the development of both sporadic and some hereditary breast tumours. Although there is no doubt that germline mutations in the TP53 gene carry a high risk of early onset breast cancer, and the gene is mutated somatically in a proportion of preinvasive and invasive breast cancers, it is not usually the initiating genetic event in most breast tumours. It does, however, seem to be an independent prognostic factor for survival and could prove useful in clinical management of node negative breast cancer patients. There has been an explosion of reports about the function of the TP53 protein--in particular, it seems to have a central role in the monitoring of some types of DNA damage. This role may prove to be the most important aspect of its association with breast cancer development, both as a prognostic factor and as a handle for treatment.
事实证明，TP53蛋白在细胞受到DNA损伤后的细胞周期控制中起着核心作用，关于其在细胞分裂调控中作用的新特性每周都有报道。TP53是人类肿瘤中最常发生改变的癌基因，与散发性和一些遗传性乳腺肿瘤的发生有关。虽然毫无疑问，TP53基因的种系突变会带来早发性乳腺癌的高风险，且该基因在一部分非浸润性和浸润性乳腺癌中会发生体细胞突变，但在大多数乳腺肿瘤中，它通常不是起始的遗传事件。然而，它似乎是一个独立的生存预后因素，可能对淋巴结阴性乳腺癌患者的临床管理有用。关于TP53蛋白功能的报道激增——特别是，它似乎在监测某些类型的DNA损伤中起核心作用。作为一个预后因素和治疗靶点，这一作用可能是其与乳腺癌发生相关的最重要方面。
