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颅内注射HER2阳性乳腺癌细胞系的增殖分类

Proliferative Classification of Intracranially Injected HER2-positive Breast Cancer Cell Lines.

作者信息

Kuroiwa Yuka, Nakayama Jun, Adachi Chihiro, Inoue Takafumi, Watanabe Shinya, Semba Kentaro

机构信息

Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.

Department of Biomolecular Profiling, Translational Research Center, Fukushima Medical University, Hikarigaoka, Fukushima 960-1295, Japan.

出版信息

Cancers (Basel). 2020 Jul 6;12(7):1811. doi: 10.3390/cancers12071811.

Abstract

HER2 is overexpressed in 25-30% of breast cancers, and approximately 30% of HER2-positive breast cancers metastasize to the brain. Although the incidence of brain metastasis in HER2-positive breast cancer is high, previous studies have been mainly based on cell lines of the triple-negative subtype, and the molecular mechanisms of brain metastasis in HER2-positive breast cancer are unclear. In the present study, we performed intracranial injection using nine HER2-positive breast cancer cell lines to evaluate their proliferative activity in brain tissue. Our results show that UACC-893 and MDA-MB-453 cells rapidly proliferated in the brain parenchyma, while the other seven cell lines moderately or slowly proliferated. Among these nine cell lines, the proliferative activity in brain tissue was not correlated with either the HER2 level or the HER2 phosphorylation status. To extract signature genes associated with brain colonization, we conducted microarray analysis and found that these two cell lines shared 138 gene expression patterns. Moreover, some of these genes were correlated with poor prognosis in HER2-positive breast cancer patients. Our findings might be helpful for further studying brain metastasis in HER2-positive breast cancer.

摘要

HER2在25% - 30%的乳腺癌中过表达,约30%的HER2阳性乳腺癌会转移至脑。尽管HER2阳性乳腺癌脑转移的发生率较高,但以往研究主要基于三阴性亚型的细胞系,HER2阳性乳腺癌脑转移的分子机制尚不清楚。在本研究中,我们使用9种HER2阳性乳腺癌细胞系进行颅内注射,以评估它们在脑组织中的增殖活性。我们的结果显示,UACC - 893和MDA - MB - 453细胞在脑实质中迅速增殖,而其他7种细胞系增殖适度或缓慢。在这9种细胞系中,脑组织中的增殖活性与HER2水平或HER2磷酸化状态均无关联。为了提取与脑定植相关的特征基因,我们进行了微阵列分析,发现这两种细胞系共有138种基因表达模式。此外,其中一些基因与HER2阳性乳腺癌患者的不良预后相关。我们的发现可能有助于进一步研究HER2阳性乳腺癌的脑转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4570/7408688/30ac1e9833f7/cancers-12-01811-g001.jpg

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