Skotheim Rolf I, Korkmaz Kemal S, Klokk Tove I, Abeler Vera M, Korkmaz Ceren G, Nesland Jahn M, Fosså Sophie D, Lothe Ragnhild A, Saatcioglu Fahri
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital and University of Oslo, Oslo, Norway.
Am J Pathol. 2003 Dec;163(6):2149-54. doi: 10.1016/S0002-9440(10)63571-7.
NKX3.1 is a homeobox gene which exhibits prostate and testis specific expression. Loss of NKX3.1 expression has been implicated in prostate development and tumorigenesis, but the role of NKX3.1 in testis biology is not known. Here we show that NKX3.1 expression is dramatically down-regulated in testicular cancer of germ cell origin. Immunohistochemical analysis on a tissue microarray containing 510 testicular tissue samples indicate that NKX3.1 is expressed at high levels in normal germ cells and in carcinoma in situ, but is sharply decreased or absent in most seminomas and all embryonal carcinomas. However, NKX3.1 is expressed in a subset of the more differentiated nonseminomas. We provide evidence that these changes in NKX3.1 protein levels are mainly due to transcriptional effects. These results suggest that NKX3.1 is essential for normal testis function and that its loss of expression is highly associated with the invasive phenotype of testicular germ cell tumors.
NKX3.1是一种同源盒基因，在前列腺和睾丸中呈特异性表达。NKX3.1表达缺失与前列腺发育及肿瘤发生有关，但NKX3.1在睾丸生物学中的作用尚不清楚。在此我们发现，NKX3.1在生殖细胞起源的睾丸癌中表达显著下调。对包含510个睾丸组织样本的组织芯片进行免疫组化分析表明，NKX3.1在正常生殖细胞和原位癌中高表达，但在大多数精原细胞瘤和所有胚胎癌中急剧降低或缺失。然而，NKX3.1在部分分化程度较高的非精原细胞瘤中表达。我们提供的证据表明，NKX3.1蛋白水平的这些变化主要是由转录效应引起的。这些结果表明，NKX3.1对正常睾丸功能至关重要，其表达缺失与睾丸生殖细胞肿瘤的侵袭性表型高度相关。
