Nek2 as a novel molecular target for the treatment of breast carcinoma
Nek2 as a novel molecular target for the treatment of breast carcinoma
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DOI：
10.1111/j.1349-7006.2008.01007.x
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发表时间：
2009-01-01
期刊：
影响因子：
5.7
通讯作者：
Hamaguchi, Michinari
中科院分区：
文献类型：
--
作者：
Tsunoda, Nobuyuki;Kokuryo, Toshio;Hamaguchi, Michinari
我们研究了丝氨酸-苏氨酸激酶家族成员Nek 2在乳腺癌致瘤性生长中的作用。通过免疫印迹，在检查的所有乳腺癌细胞系（BT 20、BT474、Hs 578 T、MCF 7、MDA-MB-231、T47 D和ZR-75-1）中观察到Nek 2表达增加。通过用Nek 2短干扰RNA（siRNA）处理，Nek 2在雌激素受体（ER）阳性（MCF 7）和ER阴性（MDA-MB-231）乳腺癌细胞系中的表达明显降低。Nek 2 siRNA处理基本上抑制了这些细胞系的细胞生长、软琼脂中的集落形成和体外侵袭力。在皮下植入MCF 7或MDA-MB-231的异种移植裸鼠模型中，与对照siRNA注射相比，在肿瘤结节周围皮下注射Nek 2 siRNA导致肿瘤尺寸减小。总之，Nek 2似乎在乳腺癌细胞的致瘤性生长中起关键作用，并且可能是用于治疗ER阳性和ER阴性病例中的乳腺癌的有用的治疗分子靶点。（Cancer Sci 2009; 100：111-116）。
We investigated the role of Nek2, a member of the serine-threonine kinase family, in the tumorigenic growth of breast carcinoma. Increased expression of Nek2 was observed in all breast carcinoma cell lines examined (BT20, BT474, Hs578T, MCF7, MDA-MB-231, T47D, and ZR-75-1) by immunoblotting. By treatment with Nek2 short interfering RNA (siRNA), expression of Nek2 was clearly decreased in both estrogen receptor (ER)-positive (MCF7) and ER-negative (MDA-MB-231) breast carcinoma cell lines. Cell growth, colony formation in soft agar, and in vitro invasiveness of these cell lines were substantially suppressed by Nek2 siRNA treatment. In a xenograft nude mouse model with subcutaneous implantation of MCF7 or MDA-MB-231, subcutaneous injection of Nek2 siRNA around the tumor nodules resulted in a reduction of tumor size compared with those of control siRNA injection. Taken together, Nek2 appears to play a pivotal role in tumorigenic growth of breast carcinoma cells, and could be a useful therapeutic molecular target for the treatment of breast carcinoma both in ER-positive and ER-negative cases. (Cancer Sci 2009; 100: 111-116).