Isolation of DICE1:: A gene frequently affected by LOH and downregulated in lung carcinomas
Isolation of DICE1:: A gene frequently affected by LOH and downregulated in lung carcinomas
复制标题
DOI：
10.1038/sj.onc.1202806
复制
发表时间：
1999-08-12
期刊：
影响因子：
8
通讯作者：
Weidle, UH
中科院分区：
文献类型：
--
作者：
Wieland, I;Arden, KC;Weidle, UH
在散发性肿瘤的发展和进展中，多个肿瘤抑制基因被失活，这可能与易感性癌基因不同。在此之前，已经在肺、头颈部、乳腺、卵巢和前列腺肿瘤中发现了一个与视网膜母细胞瘤易感基因1（RBI）不同的肿瘤抑制基因位点。通过基因组差异克隆和定位克隆相结合的方法，我们分离了位于13q14.12-14.2的新基因（DICE 1）的cDNA。DICE 1基因在进化上高度保守，其mRNA在多种胎儿和成人组织中表达，DICE 1 cDNA编码887个氨基酸的蛋白质，对应于100 kD的蛋白质，其与小鼠EGF重复跨膜蛋白DBI-1的羧基端的一半显示92.9%的同一性。DBI-1蛋白干扰对胰岛素样生长因子1（IGF-I）的促有丝分裂反应，并可能参与锚定依赖性生长。与正常肺组织相比，在所分析的大多数非小细胞肺癌中，DICE 1 mRNA的表达降低或检测不到。DICE 1基因在等位基因丢失区域的位置、其高度进化保守性以及在癌细胞中表达的下调表明，DICE 1是非小细胞肺癌以及可能在其他散发性癌中的候选抑癌基因。
In the development and progression of sporadic tumors multiple tumor suppressor genes are inactivated that may be distinct from predisposing cancer genes. Previously, a tumor suppressor locus on human chromosome 13q14 that is distinct from the retinoblastoma predisposing gene 1 (RBI) has been identified in lung, head and neck, breast, ovarian and prostate tumors, By an approach that combines genomic difference cloning and positional cloning we isolated the cDNA of a novel gene (DICE1) located at 13q14.12-14.2. The DICE1 gene is highly conserved in evolution and its mRNA is expressed in a nide variety of fetal and adult tissues, The DICE1 cDNA encodes a predicted protein of 887 amino acids corresponding to an 100 kD protein that shows 92.9% identity to the carboxy-terminal half of the mouse EGF repeat transmembrane protein DBI-1. The DBI-1 protein interferes with the mitogenic response to insulin-like growth factor 1 (IGF-I) and is presumably involved in anchorage-dependent growth. When compared to normal lung tissue expression of the DICE1 mRNA aas reduced or undetectable in the majority of non-small cell lung carcinomas analysed, The location of the DICE1 gene in the region of allelic loss, its high evolutionary conservation and the downregulation of expression in carcinoma cells suggests that DICE1 is a candidate tumor suppressor gene in non-small cell lung carcinomas and possibly in other sporadic carcinomas.