Kumar T R, Donehower L A, Bradley A, Matzuk M M
Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
J Intern Med. 1995 Sep;238(3):233-8. doi: 10.1111/j.1365-2796.1995.tb00928.x.
Tumour-suppressor genes are negative regulators of cell division and growth. Over the past decade, multiple, distinct tumour-suppressor genes have been identified and cloned. In recent years, the ability to specifically manipulate the mouse genome via overexpression, underexpression or deletion of genes using transgenic expression systems and embryonic stem cell (ES) technology has led to the identification and definition of the precise function of several tumour suppressor genes in vivo. Included in this group are mice with mutations in the p53 and retinoblastoma (Rb) genes. p53 Mutant mice are highly susceptible to tumour development and will serve as excellent models to understand the aetiology and pathology of several human cancers. In contrast to the role of the Rb gene in human retinoblastomas, mice heterozygous for a mutant Rb allele do not develop retinoblastoma, but develop pituitary tumours instead. Similar ES cell technology has been used to generate alpha-inhibin deficient mice. Inhibin-deficient mice develop gonadal and adrenal tumours with nearly 100% penetrance. These studies have identified inhibin as a novel secreted tumour suppressor. In the future, many of the unidentified functions of tumour-suppressor genes can be tested using this powerful in vivo assay system.
肿瘤抑制基因是细胞分裂和生长的负调节因子。在过去十年中，多个不同的肿瘤抑制基因已被鉴定和克隆。近年来，利用转基因表达系统和胚胎干细胞（ES）技术通过基因的过表达、低表达或缺失来特异性操纵小鼠基因组的能力，已导致体内几种肿瘤抑制基因的精确功能被鉴定和明确。这一组中包括p53基因和视网膜母细胞瘤（Rb）基因发生突变的小鼠。p53突变小鼠对肿瘤发生高度易感，将成为理解几种人类癌症病因和病理的优秀模型。与Rb基因在人类视网膜母细胞瘤中的作用不同，Rb等位基因突变的杂合子小鼠不会发生视网膜母细胞瘤，而是发生垂体肿瘤。类似的ES细胞技术已被用于生成α-抑制素缺陷小鼠。抑制素缺陷小鼠发生性腺和肾上腺肿瘤的发生率接近100%。这些研究已将抑制素确定为一种新的分泌型肿瘤抑制因子。未来，许多尚未明确的肿瘤抑制基因功能可以使用这种强大的体内检测系统进行测试。
