Hart Adam H, Hartley Lynne, Parker Karen, Ibrahim Marilyn, Looijenga Leendert H J, Pauchnik Marija, Chow Chung Wo, Robb Lorraine
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Cancer. 2005 Nov 15;104(10):2092-8. doi: 10.1002/cncr.21435.
The NANOG gene, a member of the homeobox family of DNA binding transcription factors, was recently identified in a screen for pluripotency-promoting genes. NANOG overexpression in murine embryonic stem cells is sufficient to maintain self-renewal and to block differentiation. The NANOG gene is located on human chromosome 12p13, a region frequently duplicated in human tumors of germ cell origin and in cultured human embryonic stem cells. Here we investigate the expression and gene copy number of NANOG in human germ cells and tumors of germ cell origin.
Immunohistochemistry and quantitative polymerase chain reaction (QPCR) were used to examine the expression and gene copy number of the human NANOG gene in germ cell tumors.
NANOG protein was detected in germline stem cells (gonocytes) within the developing testis. Immunohistochemistry and quantitative real-time PCR analysis were used to demonstrate that NANOG is highly and specifically expressed in carcinoma in situ (CIS), embryonal carcinomas, and seminomas, but not in teratomas and yolk sac tumors.
NANOG expression in germline stem cells (gonocytes), CIS, embryonal carcinoma, and seminoma reveals a molecular and developmental link between germ cell tumors and the embryonic cells from which they arise. Identification of NANOG as a molecular marker of undifferentiated germ cell tumors provides a novel tool for identifying and classifying tumors of germ cell origin.
NANOG基因是DNA结合转录因子同源框家族的成员，最近在一项促进多能性基因的筛选中被鉴定出来。在小鼠胚胎干细胞中过表达NANOG足以维持自我更新并阻止分化。NANOG基因位于人类染色体12p13上，该区域在人类生殖细胞起源的肿瘤和培养的人类胚胎干细胞中经常发生复制。在此，我们研究NANOG在人类生殖细胞和生殖细胞起源肿瘤中的表达及基因拷贝数。
采用免疫组织化学和定量聚合酶链反应（QPCR）检测人类NANOG基因在生殖细胞肿瘤中的表达及基因拷贝数。
在发育中的睾丸内的生殖系干细胞（生殖母细胞）中检测到NANOG蛋白。免疫组织化学和定量实时PCR分析表明，NANOG在原位癌（CIS）、胚胎癌和精原细胞瘤中高度且特异性表达，但在畸胎瘤和卵黄囊瘤中不表达。
NANOG在生殖系干细胞（生殖母细胞）、CIS、胚胎癌和精原细胞瘤中的表达揭示了生殖细胞肿瘤与其起源的胚胎细胞之间的分子和发育联系。将NANOG鉴定为未分化生殖细胞肿瘤的分子标志物为鉴定和分类生殖细胞起源的肿瘤提供了一种新工具。
