Verkerk A J, Ariel I, Dekker M C, Schneider T, van Gurp R J, de Groot N, Gillis A J, Oosterhuis J W, Hochberg A A, Looijenga L H
Laboratory of Experimental Patho-Oncology, Dr. Daniel den Hoed Cancer Center, University Hospital, Rotterdam, The Netherlands.
Oncogene. 1997 Jan 9;14(1):95-107. doi: 10.1038/sj.onc.1200802.
The expression pattern of the imprinted human H19 gene was investigated in testicular cancers of different etiology, as well as in normal testicular parenchyma, parenchyma without germ cells, and adjacent to testicular germ cell tumors of adolescents and adults (TGCTs), using RNase protection analysis, mRNA in situ hybridization and reverse-transcription polymerase chain reaction. While different total expression levels were detected in spermatocytic seminomas, lymphomas, a Sertoli cell tumor and Leydig cell tumors, none showed a disturbance of monoallelic expression. Strikingly, the majority of invasive TGCTs revealed expression of both parental alleles. The total level of expression highly correlated with differentiation lineage and stage of maturation, similar to that as reported during early normal embryogenesis. Biallelic expression could also be determined specifically in testis parenchyma containing the preinvasive lesion of this cancer. We therefore conclude that within the adult testis, biallelic H19 expression is specific for TGCTs, and that the level of expression is dependent on differentiation lineage and maturation stage. This is in agreement with the proposed primordial germ cell-origin of this cancer, and might be related to retention of embryonic characteristics in TGCTs. In addition, our data argue against H19 being a tumor suppressor gene.
利用核糖核酸酶保护分析、信使核糖核酸原位杂交和逆转录聚合酶链反应,对不同病因的睾丸癌、正常睾丸实质、无生殖细胞的实质以及青少年和成人睾丸生殖细胞肿瘤(TGCT)旁组织中印记人类H19基因的表达模式进行了研究。虽然在精母细胞性精原细胞瘤、淋巴瘤、支持细胞瘤和间质细胞瘤中检测到了不同的总表达水平,但均未显示单等位基因表达的紊乱。引人注目的是,大多数浸润性TGCT显示出两个亲本等位基因的表达。总表达水平与分化谱系和成熟阶段高度相关,类似于正常早期胚胎发育过程中所报道的情况。双等位基因表达也可以在含有该癌症浸润前病变的睾丸实质中特异性地确定。因此,我们得出结论,在成年睾丸中,双等位基因H19表达是TGCT特有的,并且表达水平取决于分化谱系和成熟阶段。这与该癌症起源于原始生殖细胞这一观点一致,并且可能与TGCT中胚胎特征的保留有关。此外,我们的数据反驳了H19是一种肿瘤抑制基因的观点。