Cooper H M, Armes P, Britto J, Gad J, Wilks A F
Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, Australia.
Oncogene. 1995 Dec 7;11(11):2243-54.
Loss of DCC gene expression has now been demonstrated in a wide variety of metastatic cancers. Here we present the nucleotide sequence and predicted amino acid sequence of mouse DCC. Mouse and human DCC share 96% identity at the amino acid level. Analysis of DCC mRNA expression throughout the mid and late stages of gestation in the mouse, demonstrated that DCC mRNA is expressed at significantly higher levels in the developing mouse embryo than in any adult tissue. In addition, we show that an embryo-specific, alternatively spliced, form of DCC is expressed in day 9.5 through day 18.5 embryos. The expression of both alternatively spliced forms of DCC is developmentally regulated such that the embryonic form of DCC predominates in day 9.5 and 10.5 embryos. In the later stage embryos the expression of this alternatively spliced form of DCC is down-regulated with respect to that of the adult form. Whole-mount in situ hybridization of day 11.5 mouse embryos revealed that DCC mRNA is expressed at high levels in the developing brain and the neural tube. However, no DCC mRNA could be detected in any other embryonic tissue at this stage of development. These observations suggest that during embryogenesis DCC may play a pivotal role in the development of the central nervous system.
现已证实在多种转移性癌症中存在DCC基因表达缺失的情况。在此,我们展示小鼠DCC的核苷酸序列和预测的氨基酸序列。小鼠和人类DCC在氨基酸水平上有96%的同一性。对小鼠妊娠中后期DCC mRNA表达的分析表明,DCC mRNA在发育中的小鼠胚胎中的表达水平明显高于任何成年组织。此外,我们发现一种胚胎特异性的、可变剪接的DCC形式在9.5天至18.5天的胚胎中表达。DCC两种可变剪接形式的表达均受到发育调控,使得DCC的胚胎形式在9.5天和10.5天的胚胎中占主导。在后期胚胎中,这种可变剪接形式的DCC相对于成年形式的表达下调。对11.5天小鼠胚胎进行的全胚胎原位杂交显示,DCC mRNA在发育中的脑和神经管中高水平表达。然而,在发育的这个阶段,在任何其他胚胎组织中均未检测到DCC mRNA。这些观察结果表明,在胚胎发生过程中,DCC可能在中枢神经系统的发育中起关键作用。