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神经调节蛋白-1刺激乳腺癌患者血清DJ-1升高。

NRG-1 Stimulates Serum DJ-1 Increase in Breast Cancers.

作者信息

Wang Yuandong, Zhang Yan, Lu Qian, Wang Yiming, Sun Xinchen, Zhang Shu

机构信息

Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, China.

出版信息

Pathol Oncol Res. 2019 Jan;25(1):71-79. doi: 10.1007/s12253-017-0326-z. Epub 2017 Sep 30.

Abstract

To explore the relationship between the expression of DJ-1/HER3 and tumor grade in breast cancer, and investigate the effect of HER3 on NRG-1-mediated serum DJ-1 level in vivo. We analyze the expression level of DJ-1 and HER3 in 68 patients with different grades of breast cancer by immunostaining the tissue microarray. Besides, we investigated the serum DJ-1 level by ELISA. We found that the detectable DJ-1 protein expression is decreased, and the HER3 expression is increased in tumor tissue with the progression of breast cancer. There is a significant rise of DJ-1 in serum in vivo with the stimulation of NRG-1. Meanwhile, we found that HER3 knockdown abolishes NRG-1-induced serum DJ-1 increase and HER3 overexpress improves NRG-1-induced serum DJ-1 increase. This study provides a serum biomarker for breast cancer. The results showed that DJ-1 was associated with clinical stage of breast cancer, and NRG-1 increased the dissociation of HER3 and DJ-1, with promoting the level of DJ-1 in peripheral blood. It is suggested that the level of DJ-1 in peripheral blood may be conducive to assess the prognosis of patients with breast cancer and serum DJ-1 levels can serve as an indicator of therapeutic effectiveness for the development of HER3 targeting breast cancer antibody therapies.

摘要

为了探究DJ-1/HER3的表达与乳腺癌肿瘤分级之间的关系,并研究HER3对体内NRG-1介导的血清DJ-1水平的影响。我们通过对组织芯片进行免疫染色,分析了68例不同分级乳腺癌患者中DJ-1和HER3的表达水平。此外,我们通过ELISA法检测血清DJ-1水平。我们发现,随着乳腺癌病情进展,肿瘤组织中可检测到的DJ-1蛋白表达降低,而HER3表达增加。在体内,NRG-1刺激可使血清DJ-1显著升高。同时,我们发现敲低HER3可消除NRG-1诱导的血清DJ-1升高,而过表达HER3则可增强NRG-1诱导的血清DJ-1升高。本研究为乳腺癌提供了一种血清生物标志物。结果表明,DJ-1与乳腺癌的临床分期相关,NRG-1增加了HER3与DJ-1的解离,从而促进外周血中DJ-1水平升高。提示外周血DJ-1水平可能有助于评估乳腺癌患者的预后,血清DJ-1水平可作为HER3靶向性乳腺癌抗体治疗疗效的指标。

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