Caricasole A A, van Schaik R H, Zeinstra L M, Wierikx C D, van Gurp R J, van den Pol M, Looijenga L H, Oosterhuis J W, Pera M F, Ward A, de Bruijn D, Kramer P, de Jong F H, van den Eijnden-van Raaij A J
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Oncogene. 1998 Jan 8;16(1):95-103. doi: 10.1038/sj.onc.1201515.
We describe the cloning and initial characterization of a novel cDNA from human embryonal carcinoma (EC) cells. This cDNA, which we named human growth differentiation factor 3 (hGDF3), encodes the homologue of mouse GDF3, a TGFbeta superfamily member belonging to the Growth/Differentiation Factors. We have analysed the expression of hGDF3 in human embryonal carcinoma cell lines and in primary testicular germ cell tumours of adolescents and adults (TGCTs). Expression of hGDF3 in human EC cell lines is stem cell-specific, is down-regulated upon RA-mediated differentiation and is increased upon culture of the cells in the presence of activin A. In TGCTs, hGDF3 expression is low in seminomas, while expression in non-seminomas is readily detectable and appears to be associated with the EC and yolk sac components in the tumours. We have also mapped the hGDF3 locus to the short arm of human chromosome 12, a region consistently overrepresented in human testicular germ cell tumours. Thus, hGDF3 represents an embryonal carcinoma stem cell-associated marker both in vitro and in vivo.
我们描述了从人胚胎癌（EC）细胞中克隆出的一种新型cDNA及其初步特征。这种cDNA，我们将其命名为人生长分化因子3（hGDF3），编码小鼠GDF3的同源物，GDF3是转化生长因子β（TGFβ）超家族中属于生长/分化因子的一员。我们分析了hGDF3在人胚胎癌细胞系以及青少年和成人原发性睾丸生殖细胞肿瘤（TGCTs）中的表达情况。hGDF3在人EC细胞系中的表达具有干细胞特异性，在视黄酸（RA）介导的分化过程中表达下调，而在细胞于激活素A存在的情况下培养时表达增加。在TGCTs中，hGDF3在精原细胞瘤中的表达较低，而在非精原细胞瘤中的表达易于检测到，并且似乎与肿瘤中的EC和卵黄囊成分相关。我们还将hGDF3基因座定位到人类12号染色体的短臂上，该区域在人类睾丸生殖细胞肿瘤中一直过度表达。因此，hGDF3在体外和体内均代表一种胚胎癌干细胞相关标志物。
