NOTCH4 is a potential therapeutic target for triple-negative breast cancer.
NOTCH4 is a potential therapeutic target for triple-negative breast cancer.
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DOI：
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发表时间：
2014
影响因子：
2
通讯作者：
Iori Nagamatsu;H. Onishi;S. Matsushita;M. Kubo;M. Kai;A. Imaizumi;K. Nakano;M. Hattori;Y. Oda;Masao Tanaka;M. Katano
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文献类型：
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作者：
Iori Nagamatsu;H. Onishi;S. Matsushita;M. Kubo;M. Kai;A. Imaizumi;K. Nakano;M. Hattori;Y. Oda;Masao Tanaka;M. Katano
背景/目标是三阴性乳腺癌（TNBC）的预后很差。在本研究中，我们评估了Notch4受体是否是TNBC的潜在新治疗靶标。在具有或不带小互干的RNA（siRNA）的Notch4，有或没有Notch4质粒转染的TNBC细胞中评估了体外增殖和侵袭性的材料和方法。在体内，将具有或没有Notch4 siRNA的MDA-MB-231细胞皮下植入小鼠的侧面区域。 Notch4的核转运频率通过免疫组织化学评估21个TNBC样品和46个非TNBC样品。结果NOTCH4在TNBC细胞中的抑制作用降低了增殖和侵袭性，TNBC细胞中Notch4的过表达增加了增殖和侵入性。 NOTCH4抑制减少了小鼠异种移植物的肿瘤体积和肿瘤性。与其他细胞相比，TNBC细胞的Notch4核转运频率更高。结论Notch4是三阴性乳腺癌的新潜在治疗靶标。
BACKGROUND/AIM The prognosis for triple-negative breast cancer (TNBC) is poor. In the present study, we evaluated whether NOTCH4 receptor is a potential new therapeutic target for TNBC. MATERIALS AND METHODS In vitro proliferation and invasiveness were evaluated in TNBC cells with or without small-interfering RNA (siRNA) for NOTCH4, and with or without NOTCH4 plasmid transfection. In vivo, MDA-MB-231 cells with or without NOTCH4 siRNA were subcutaneously implanted into the flank regions of mice. The frequency of nuclear translocation of NOTCH4 was assessed by immunohistochemistry in 21 TNBC samples and 46 non-TNBC samples. RESULTS NOTCH4 inhibition in TNBC cells reduced proliferation and invasiveness, and NOTCH4 overexpression in TNBC cells increased proliferation and invasiveness. NOTCH4 inhibition reduced tumour volume and tumourigenicity of mouse xenografts. TNBC cells had a higher frequency of nuclear translocation of NOTCH4 than other cells. CONCLUSION NOTCH4 is a new potential therapeutic target for triple-negative breast cancer.