Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression.
Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression.
复制标题
DOI：
--
复制
发表时间：
2000-11
期刊：
影响因子：
11.2
通讯作者：
C. Bowen;L. Bubendorf;H. Voeller;R. Slack;N. Willi;G. Sauter;Th. Gasser;P. Koivisto;E. Lack-E.
中科院分区：
文献类型：
--
作者：
C. Bowen;L. Bubendorf;H. Voeller;R. Slack;N. Willi;G. Sauter;Th. Gasser;P. Koivisto;E. Lack-E.
NKX3.1是位于染色体8 p21上的前列腺特异性同源异型盒基因。在小鼠中，Nkx3.1对前列腺上皮具有生长抑制和分化作用。在人类前列腺癌中未发现NKX3.1编码区的突变，未能支持NKX3.1是肿瘤抑制基因的观点。为了研究NKX3.1蛋白在人组织和前列腺癌中的表达，我们制备了纯化的重组NKX3.1的兔抗血清。在正常人体组织中，NKX3.1表达见于睾丸、罕见的肺粘液腺和输尿管移行上皮的孤立区域。NKX3.1在61例前列腺癌根治术标本的正常前列腺上皮细胞核中均匀表达。我们分析了507例前列腺上皮肿瘤样本，其中大部分包含在组织微阵列中，该微阵列包含来自不同阶段的前列腺肿瘤样本。我们在5%的良性前列腺增生、20%的高级别前列腺上皮内瘤变、6%的T1 a/B样本、22%的T34样本、34%的难治性前列腺癌和78%的转移瘤中观察到NKX3.1表达完全缺失。我们的数据表明，NKX3.1的表达是高度，但不是唯一的，具体的前列腺。NKX3.1表达缺失与前列腺癌的难治性疾病和晚期肿瘤密切相关（P < 0.0001）。
NKX3.1 is a prostate-specific homeobox gene located on chromosome 8p21. In the mouse, Nkx3.1 has growth-suppressive and differentiating effects on prostatic epithelium. Mutations of the coding region of NKX3.1 were not found in human prostate cancer, failing to support the notion that NKX3.1 was a tumor suppressor gene. To study the expression o NKX3.1 protein in human tissues and prostate cancer, we derived a rabbit antiserum against purified recombinant NKX3.1. Among normal human tissues, NKX3.1 expression was seen in testis, in rare pulmonary mucous glands, and in isolated regions of transitional epithelium of the ureter. NKX3.1 was uniformly expressed in nuclei of normal prostate epithelial cells in 61 histological sections from radical prostatectomy specimens. We analyzed 507 samples of neoplastic prostate epithelium, most of which were contained on a tissue microarray that contained samples from different stages of prostatic neoplasia. We observed complete loss of NKX3.1 expression in 5% of benign prostatic hyperplasias, 20% of high-grade prostatic intraepithelial neoplasias, 6% of T1a/b samples, 22% of T3/4 samples, 34% of hormone-refractory prostate cancers, and 78% of metastases. Our data show that NKX3.1 expression is highly, but not exclusively, specific for the prostate. Loss of NKX3.1 expression is strongly associated with hormone-refractory disease and advanced tumor stage in prostate cancer (P < 0.0001).