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NKD1基因下调与乳腺浸润性导管癌的不良预后相关。

NKD1 down-regulation is associated with poor prognosis in breast invasive ductal carcinoma.

作者信息

Lv Zhi-Dong, Zhang Lin, Liu Xiang-Ping, Jin Li-Ying, Dong Qian, Li Fu-Nian, Wang Hai-Bo, Kong Bin

机构信息

Department of Breast Surgery, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.

Department of Central Laboratory of Molecular Biology, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.

出版信息

Int J Clin Exp Pathol. 2015 Apr 1;8(4):4015-21. eCollection 2015.

Abstract

As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression and clinicopathological significance of NKD1 in patients with breast cancer is still unclear. The aim of this study was to evaluate NKD1 expression in breast cancer and to investigate the question of whether reduced expression of NKD1 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of NKD1 and relevance with clinicopathological factors in the breast invasive ductal carcinoma. Reduction of NKD1 was significantly correlated with lymph node metastasis, histological grade and ER expression in breast cancer. Patients with negative NKD1 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive NKD1 expression. This interpretation is in keeping with the results obtained from our in vitro experiments on MDA-MB-231 cells, we demonstrated that upregulation of NKD1 expression by infect with an adenovirus containing a NKD1 vector significantly reduced the migration of breast cancer cells. These data suggest that NKD1 plays an important role in invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.

摘要

作为经典Wnt信号通路的负性调节因子,裸蛋白1(NKD1)在许多正常组织中广泛表达。然而,NKD1在乳腺癌患者中的表达及临床病理意义仍不清楚。本研究的目的是评估NKD1在乳腺癌中的表达,并探讨NKD1表达降低在乳腺癌发生或进展中是否具有任何病理意义。在本研究中,我们进行了蛋白质印迹法和免疫组织化学,以评估NKD1在乳腺浸润性导管癌中的表达及其与临床病理因素的相关性。NKD1表达降低与乳腺癌的淋巴结转移、组织学分级和雌激素受体(ER)表达显著相关。NKD1表达阴性的患者术后5年累积生存率显著低于NKD1表达阳性的患者。这一解释与我们在MDA-MB-231细胞上进行的体外实验结果一致,我们证明用含有NKD1载体的腺病毒感染上调NKD1表达可显著降低乳腺癌细胞的迁移。这些数据表明,NKD1在人类乳腺癌侵袭中起重要作用,它似乎是乳腺癌患者的一个潜在预后标志物。

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