TYRO3 as a potential therapeutic target in breast cancer.
TYRO3 as a potential therapeutic target in breast cancer.
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DOI：
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发表时间：
2014-07
影响因子：
2
通讯作者：
R. C. Ekyalongo;T. Mukohara;Y. Funakoshi;H. Tomioka;Y. Kataoka;Y. Shimono;N. Chayahara;M. Toyoda;N. Kiyota;H. Minami
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作者：
R. C. Ekyalongo;T. Mukohara;Y. Funakoshi;H. Tomioka;Y. Kataoka;Y. Shimono;N. Chayahara;M. Toyoda;N. Kiyota;H. Minami
目的 我们评估了 TYRO3 作为各种类型乳腺癌细胞系治疗靶点的潜力。材料和方法 通过小干扰 RNA (siRNA) 敲低 TYRO3 对四种雌激素受体 (ER) 阳性/HER2 非扩增（管腔型）、两种 ER 阴性/HER2 扩增（HER2 型）和两种 ER 阴性/HER2 非扩增（三阴性 [TN] 型）细胞系的增殖、细胞周期分布和细胞信号传导的影响比较。结果虽然 TYRO3 敲低在 luminal 型细胞中引起最大的增殖抑制，在 HER2 型细胞中诱导较小程度的增殖抑制，但在 TN 型细胞中没有观察到增殖抑制。在富含雌二醇 (E2) 和无雌二醇 (E2) 的条件下均观察到 TYRO3 siRNA 诱导的管腔型细胞增殖抑制。增殖抑制与 G0-G1/S 细胞周期停滞相关。蛋白质印迹分析显示，仅在对 TYRO3 敲低敏感的细胞系中，ERK1/2 或 STAT3 以及细胞周期蛋白 D1 的磷酸化降低。结论 TYRO3 是乳腺癌的潜在治疗靶点，特别是管腔型细胞。
AIM We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cancer cell lines. MATERIALS AND METHODS The effects of TYRO3-knockdown by small interfering RNA (siRNA) on proliferation, cell-cycle distribution, and cell signaling in four estrogen receptor (ER)-positive/HER2-non-amplified (luminal-type), two ER-negative/HER2-amplified (HER2-type), and two ER-negative/HER2-non-amplified (triple negative [TN]-type) cell lines were compared. RESULTS Whereas TYRO3 knockdown induced the greatest proliferation suppression in luminal-type cells, and to a lesser extent in HER2-type cells, no proliferation inhibition was observed in TN-type cells. The TYRO3 siRNA-induced proliferation inhibition in luminal-type cells was observed in both estradiol (E2)-rich and -null conditions. The proliferation suppression was correlated with G0-G1/S cell-cycle arrest. Western blot analysis showed a decrease in phosphorylation of ERK1/2 or STAT3, and in cyclin D1 only in cell lines sensitive to TYRO3-knockdown. CONCLUSION TYRO3 is a potential therapeutic target in breast cancer, particularly in luminal-type cells.