Wei Hong, Wang Hongbin, Ji Qiao, Sun Jiawei, Tao Lin, Zhou Xianli
Department of Ultrasonography, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People's Republic of China.
Onco Targets Ther. 2015 Dec 14;8:3721-30. doi: 10.2147/OTT.S89779. eCollection 2015.
Nuclear receptor binding protein 1 (NRBP1) is a highly conserved protein that is ubiquitously expressed across cell types in humans. NRBP1 has been recently identified as an adaptor protein. It has been suggested that it plays important roles in cellular homeostasis and the pathophysiology of cancer. To determine whether NRBP1 is involved in the pathophysiology of breast cancer, we performed a correlation study between the expression level of NRBP1 and the clinicopathological features in 92 breast cancer patients. A strong correlation was detected between NRBP1 expression and advanced histopathology grades, tumor, node, and metastasis stage, tumor diameter, lymph node involvement, as well as the recurrence of breast cancer in 92 tested patients. The tumor tissues from patients also expressed lower NRBP1 than did adjacent healthy tissues. Furthermore, we overexpressed NRBP1 in MCF-7 and MDA-MB-231 breast cancer cell lines and found NRBP1 upregulation-inhibited cell proliferation by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Blocking the autocrine Wnt signaling pathway by LGK974 could remove the NRBP1-overexpression-induced inhibition in breast cancer cells. The results of this study suggest that NRBP1 plays a tumor-suppressive role in breast cancer pathophysiology, which likely acts through the Wnt/β-catenin signaling pathway.
核受体结合蛋白1（NRBP1）是一种高度保守的蛋白质，在人类的各种细胞类型中普遍表达。NRBP1最近被鉴定为一种衔接蛋白。有人认为它在细胞稳态和癌症病理生理学中发挥重要作用。为了确定NRBP1是否参与乳腺癌的病理生理学，我们对92例乳腺癌患者的NRBP1表达水平与临床病理特征进行了相关性研究。在92例受试患者中，检测到NRBP1表达与高级组织病理学分级、肿瘤、淋巴结和转移分期、肿瘤直径、淋巴结受累以及乳腺癌复发之间存在强烈相关性。患者的肿瘤组织中NRBP1的表达也低于相邻的健康组织。此外，我们在MCF-7和MDA-MB-231乳腺癌细胞系中过表达NRBP1，并通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐试验发现NRBP1上调抑制细胞增殖。用LGK974阻断自分泌Wnt信号通路可以消除NRBP1过表达诱导的对乳腺癌细胞的抑制作用。本研究结果表明，NRBP1在乳腺癌病理生理学中发挥肿瘤抑制作用，可能通过Wnt/β-连环蛋白信号通路起作用。
