Zhang Peng, Chen Yiying, Gong Miaomiao, Zhuang Zhumei, Wang Yueyue, Mu Lin, Wang Tianjiao, Pan Jinjin, Liu Yanan, Xu Jianming, Liang Rui, Yuan Yuhui
Department of General Surgery, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Cell Physiol Biochem. 2018;50(1):52-65. doi: 10.1159/000493957. Epub 2018 Oct 16.
BACKGROUND/AIMS: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear.
Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry.
Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth.
This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma.
背景/目的：HER2与乳腺肿瘤发生以及肿瘤的侵袭性生长和转移有关。其过表达与乳腺癌患者的不良预后和化疗耐药相关。尽管Grb2相关结合蛋白2（Gab2）在人类癌症的发生和发展中起重要作用，但其在HER2过表达乳腺癌中的作用及机制尚不清楚。
采用克隆形成实验和MTT实验检测细胞增殖。为检测Gab2对乳腺癌细胞干性的影响，我们使用了流式细胞术、成球实验、实时定量PCR和蛋白质免疫印迹法。建立动物模型以验证Gab2在体内对肿瘤生长的影响。通过免疫组织化学分析组织切片。
敲低Gab2可抑制PI3K/AKT和MAPK/ERK信号通路活性。敲除Gab2也降低了HER2过表达乳腺癌细胞的干性。在体内，敲低Gab2可抑制肿瘤生长。
本研究揭示了Gab2在HER2过表达乳腺癌细胞中的潜在作用。Gab2可能是HER2过表达乳腺癌临床治疗中的一个潜在靶点。
