Chang F, Syrjänen S, Syrjänen K
Department of Pathology, University of Kuopio, Finland.
J Clin Oncol. 1995 Apr;13(4):1009-22. doi: 10.1200/JCO.1995.13.4.1009.
The p53 gene encompasses 16 to 20 kb of DNA on the short arm of human chromosome 17. It encodes for a 393-amino acid nuclear phosphoprotein involved in cell-cycle control. Loss of normal p53 function is associated with cell transformation in vitro and development of neoplasms in vivo. During the past few years, the dramatic progress in the molecular biology of p53 has raised the exciting prospect for cancer management. The purpose of this review is to assess the potential role of p53 in clinical oncology.
Data on the alterations in the p53 gene in human cancers, with special emphasis on the clinical implications of changes in the p53 gene in the pathogenesis, diagnosis, prognosis, and therapy of human cancers, are summarized in this review.
Current evidence suggests that abrogation of normal p53 pathway is a common feature in human cancers, and it appears to be a critical step in the pathogenesis and progression of tumors. Analysis of p53 function and mutations in human cancers may lead to identification of the precise nature of the carcinogenic damage in human tissues. These laboratory investigations and biologic findings have raised the possibility to screen patients at increased risk for cancer, aid the diagnosis made by traditional methods, assess the prognosis of individual cancer patient, design treatment protocols, and test the response to therapeutic agents.
p53基因位于人类17号染色体短臂上，包含16至20kb的DNA。它编码一种参与细胞周期调控的393个氨基酸的核磷蛋白。正常p53功能的丧失与体外细胞转化及体内肿瘤发生相关。在过去几年中，p53分子生物学的显著进展为癌症治疗带来了令人兴奋的前景。本综述的目的是评估p53在临床肿瘤学中的潜在作用。
本综述总结了人类癌症中p53基因改变的数据，特别强调了p53基因变化在人类癌症发病机制、诊断、预后和治疗中的临床意义。
目前的证据表明，正常p53通路的废除是人类癌症的一个共同特征，并且似乎是肿瘤发病机制和进展中的关键步骤。对人类癌症中p53功能和突变的分析可能有助于确定人类组织中致癌损伤的确切性质。这些实验室研究和生物学发现增加了对癌症高危患者进行筛查、辅助传统方法诊断、评估个体癌症患者预后、设计治疗方案以及测试对治疗药物反应的可能性。
