Oliveira Andre M, Ross Jeffrey S, Fletcher Jonathan A
Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
Am J Clin Pathol. 2005 Dec;124 Suppl:S16-28. doi: 10.1309/5XW3L8LU445QWGQR.
Tumor suppressor genes encode for proteins whose normal function is to inhibit cell transformation and whose inactivation is advantageous for tumor cell growth and survival. A variety of mechanisms result in the inactivation of tumor suppressor genes, including intragenic mutations, chromosomal deletions, and loss of expression by methylation-mediated transcriptional silencing or increased proteolysis. Tumor suppressor genes participate in a variety of critical and highly conserved cell functions, including regulation of the cell cycle and apoptosis, differentiation, surveillance of genomic integrity and repair of DNA errors, signal transduction, and cell adhesion. Tumor suppressor functions can be separated into 2 major categories: gatekeepers and caretakers. Gatekeepers directly inhibit tumor growth or promote tumor death. Inactivation of these genes contributes directly to cancer formation and progression. Among them, the p53 gene is the most well known. Located on chromosome band 17p13, p53 encodes a 53-kd multifunctional transcription factor that regulates the expression of genes involved in cell cycle control, apoptosis, DNA repair, and angiogenesis. In breast cancer, most studies have shown that p53 mutation or down-regulation is associated with adverse prognosis. Other tumor suppressor genes of interest in breast cancer include the retinoblastoma gene (pRb), PTEN, p16, nm23, and maspin.
肿瘤抑制基因编码的蛋白质，其正常功能是抑制细胞转化，而其失活有利于肿瘤细胞的生长和存活。多种机制可导致肿瘤抑制基因失活，包括基因内突变、染色体缺失以及通过甲基化介导的转录沉默或蛋白水解增加导致的表达缺失。肿瘤抑制基因参与多种关键且高度保守的细胞功能，包括细胞周期调控、凋亡、分化、基因组完整性监测和DNA错误修复、信号转导以及细胞黏附。肿瘤抑制功能可分为两大类：门卫基因和守护者基因。门卫基因直接抑制肿瘤生长或促进肿瘤死亡。这些基因的失活直接导致癌症的形成和进展。其中，p53基因最为人所知。p53位于染色体17p13带上，编码一种53-kd的多功能转录因子，该因子调节参与细胞周期控制、凋亡、DNA修复和血管生成的基因的表达。在乳腺癌中，大多数研究表明p53突变或下调与不良预后相关。乳腺癌中其他感兴趣的肿瘤抑制基因包括视网膜母细胞瘤基因（pRb）、PTEN、p16、nm23和maspin。
