Activation of SNAT1/SLC38A1 in human breast cancer: correlation with p-Akt overexpression.

Activation of SNAT1/SLC38A1 in human breast cancer: correlation with p-Akt overexpression.
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DOI:
10.1186/1471-2407-13-343
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发表时间:
2013-07-12
期刊:
影响因子:
3.8
通讯作者:
Yu G
Yu G
中科院分区:
医学2区
文献类型:
--
作者:
Wang K;Cao F;Fang W;Hu Y;Chen Y;Ding H;Yu G

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SNAT 1是氨基酸转运系统A的一个亚型,它在癌症的发生和发展中发挥着潜在的作用,但它在乳腺癌中的作用仍不清楚。本研究通过检测SNAT 1在乳腺癌中的表达,探讨其促进乳腺癌发生的可能机制。采用RT-PCR和Western blotting方法检测SNAT 1在乳腺癌细胞系和新鲜组织中的转录和蛋白水平。构建了包含从210名患者获得的乳腺癌标本的组织微阵列块。使用免疫组织化学研究分析这些标本中SNAT 1的表达。SNAT 1-shRNA下调乳腺癌细胞中SNAT 1的表达,并检测其功能意义。SNAT 1在乳腺癌细胞系和乳腺癌组织中表达上调。127例(60.5%)SNAT 1过表达。SNAT 1的表达与肿瘤大小、淋巴结转移、疾病晚期、Ki-67和ER状态显著相关。内源性SNAT 1的抑制导致4 T1细胞生长抑制、细胞周期停滞和凋亡,并降低Akt的磷酸化水平。在人乳腺癌样品中,SNAT 1表达与p-Akt表达显著相关。Akt信号通路与SNAT 1之间的相互作用可能在乳腺癌的发生发展中起着重要作用,为寻找新的诊断标志物和治疗乳腺癌的新靶点提供了重要的分子基础。
SNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear. In present study, we detected SNAT1 expression in breast cancers and explored its underlying mechanism in promoting breast carcinogenesis. RT-PCR and Western blotting were performed to analyze the transcription and protein levels of SNAT1 in breast cancer cell lines and fresh tissues. Tissue microarray blocks containing breast cancer specimens obtained from 210 patients were constructed. Expression of SNAT1 in these specimens was analyzed using immunohistochemical studies. SNAT1 was down-regulated by SNAT1-shRNA in breast cancer cells and the functional significance was measured. SNAT1 was up-regulated in breast cancer cell lines and breast cancer tissues. Overexpression of SNAT1 was observed in 127 cases (60.5%). Expression of SNAT1 was significantly associated with tumor size, nodal metastasis, advanced disease stage, Ki-67, and ER status. Suppression of endogenous SNAT1 leads to cell growth inhibition, cell cycle arrest, and apoptosis of 4T1 cells and lowered the phosphorylation level of Akt. SNAT1 expression correlated significantly with p-Akt expression in human breast cancer samples. The cross-talk between Akt signaling and SNAT1 might play a critical role in the development and progression of breast cancer, providing an important molecular basis for novel diagnostic markers and new attractive targets in the treatment of breast cancer patients.
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