Kinzler K W, Ruppert J M, Bigner S H, Vogelstein B
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Nature. 1988 Mar 24;332(6162):371-4. doi: 10.1038/332371a0.
Many studies have established that a select subset of normal cellular genes are altered in cancer by point mutations, translocations or gene amplification. However, the vast majority of genetic changes that occur in neoplastic cells have not yet been identified. In an attempt to identify some of these other genetic changes, we have recently isolated a gene, GLI, by virtue of its amplification in a human glioblastoma. Subsequently, GLI was found to be amplified in other human glioblastomas (ref. 3 and unpublished data). To understand better the role of GLI in human neoplasia, we have now cloned the GLI complementary DNA (cDNA) and determined its nucleotide sequence. Analysis of the predicted translation product reveals that it contains five repeats of a DNA binding consensus sequence (zinc finger) originally described in Xenopus Transcription Factor III A (TFIIIA). Furthermore, these zinc fingers contain sequence elements that suggest the GLI gene product is a member of the recently described Kruppel family of zinc finger proteins. Additional experiments demonstrate that GLI is an evolutionarily conserved gene that is expressed in embryonal carcinoma cells but not in most adult tissues. The link between the developmentally important Kruppel family of genes and GLI is interesting considering the similarities between developing embryonic and neoplastic tissue.
许多研究已证实，正常细胞基因中的一个特定亚群在癌症中会因点突变、易位或基因扩增而发生改变。然而，肿瘤细胞中发生的绝大多数基因变化尚未被识别。为了识别其中一些其他基因变化，我们最近通过在人胶质母细胞瘤中的扩增分离出了一个基因GLI。随后，发现GLI在其他人类胶质母细胞瘤中也有扩增（参考文献3及未发表数据）。为了更好地理解GLI在人类肿瘤形成中的作用，我们现在克隆了GLI互补DNA（cDNA）并确定了其核苷酸序列。对预测的翻译产物的分析表明，它包含最初在非洲爪蟾转录因子IIIA（TFIIIA）中描述的DNA结合共有序列（锌指）的五个重复序列。此外，这些锌指包含的序列元件表明GLI基因产物是最近描述的锌指蛋白Kruppel家族的成员。进一步的实验表明，GLI是一个在进化上保守的基因，在胚胎癌细胞中表达，但在大多数成年组织中不表达。考虑到发育中的胚胎组织和肿瘤组织之间的相似性，发育上重要的Kruppel基因家族与GLI之间的联系很有趣。
