Division of Cancer Differentiation, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Biochem Biophys Res Commun. 2012 Feb 10;418(2):199-204. doi: 10.1016/j.bbrc.2011.10.123. Epub 2011 Oct 31.
Nanog, a homeodomain transcription factor, is an essential regulator for promotion of self-renewal of embryonic stem cells and inhibition of their differentiation. It has been demonstrated that nanog1 as well as nanogp8, a retrogene of nanog1, is preferentially expressed in advanced stages of several types of cancer, suggesting their involvement during cancer progression. Here, we investigated the expression of Nanog in well-characterized colon cancer cell lines. Expression of Nanog was detectable in 5 (HCT116, HT29, RKO, SW48, SW620) out of seven cell lines examined. RNA expression analyses of nanog1 and nanogp8 indicated that, while nanog1 was a major form in SW620 as well as in teratoma cells Tera-2, nanogp8 was preferentially expressed in HT29 and HCT116. In accordance with this, shRNA-mediated knockdown of nanog1 caused the reduction of Nanog in SW620 but not in HT29. Inhibition of Nanog in SW620 cells negatively affected cell proliferation and tumor formation in mouse xenograft. Biochemical subcellular fractionation and immunostaining analyses revealed predominant localization of Nanog in cytoplasm in SW620 and HT29, while it was mainly localized in nucleus in Tera-2. Our data indicate that nanog1 and nanogp8 are differentially expressed in colon cancer cells, and suggest that their expression contributes to proliferation of colon cancer cells.
Nanog 是一种同源域转录因子，是促进胚胎干细胞自我更新和抑制其分化的重要调节因子。已经证明，nanog1 及其反转录基因 nanogp8 在几种类型癌症的晚期优先表达，表明它们在癌症进展过程中参与其中。在这里，我们研究了 Nanog 在经过充分表征的结肠癌细胞系中的表达。在 7 个细胞系中，有 5 个（HCT116、HT29、RKO、SW48、SW620）检测到 Nanog 的表达。对 nanog1 和 nanogp8 的 RNA 表达分析表明，虽然 nanog1 是 SW620 以及畸胎瘤细胞 Tera-2 的主要形式，但 nanogp8 在 HT29 和 HCT116 中优先表达。与此一致的是，shRNA 介导的 nanog1 敲低导致 SW620 中 Nanog 的减少，但 HT29 中没有。SW620 细胞中 Nanog 的抑制对小鼠异种移植中的细胞增殖和肿瘤形成产生负面影响。生化亚细胞分离和免疫染色分析表明，Nanog 在 SW620 和 HT29 中的主要定位在细胞质中，而在 Tera-2 中主要定位在细胞核中。我们的数据表明，nanog1 和 nanogp8 在结肠癌细胞中差异表达，并表明它们的表达有助于结肠癌细胞的增殖。
