Weinberg R A
Department of Biology, Massachusetts Institute of Technology, Whitehead Institute of Biomedical Research, Cambridge 02142.
Ciba Found Symp. 1989;142:99-105; discussion 106-11.
Retinoblastomas and osteosarcomas in humans are associated with the homozygous inactivation of the Rb gene which maps to a locus on chromosome 13q14. This gene has been isolated as molecular clones. The gene encodes a protein of 105 kDa which is a nuclear DNA-binding phosphoprotein. The protein is not found in 15 retinoblastomas studied so far. An independent line of work examining the transforming mechanisms of the adenovirus E1A oncogene has shown that its encoded oncoprotein complexes with the Rb-encoded p105 in virus-transformed cells. This suggests that the Rb protein acts at a central intersection in the cell's growth regulatory network. Its alteration by genetic or epigenetic mechanisms appears to represent a critical event in several different pathways of tumorigenesis.
人类视网膜母细胞瘤和骨肉瘤与Rb基因的纯合失活有关，该基因定位于13号染色体q14区域。该基因已被分离为分子克隆。该基因编码一种105 kDa的蛋白质，它是一种核DNA结合磷蛋白。在迄今为止研究的15例视网膜母细胞瘤中未发现这种蛋白质。另一项研究腺病毒E1A癌基因转化机制的独立工作表明，其编码的癌蛋白在病毒转化细胞中与Rb编码的p105形成复合物。这表明Rb蛋白在细胞生长调节网络的一个中心交叉点起作用。其通过遗传或表观遗传机制的改变似乎代表了几种不同肿瘤发生途径中的关键事件。
