Stratifin accelerates progression of lung adenocarcinoma at an early stage.
Stratifin accelerates progression of lung adenocarcinoma at an early stage.
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DOI：
10.1186/s12943-015-0414-1
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发表时间：
2015-07-30
期刊：
影响因子：
37.3
通讯作者：
Noguchi M
中科院分区：
文献类型：
--
作者：
Shiba-Ishii A;Kim Y;Shiozawa T;Iyama S;Satomi K;Kano J;Sakashita S;Morishita Y;Noguchi M
肺原位腺癌（AIS）的预后非常好。然而，早期但浸润性腺癌（eIA）有时具有致命的结局。我们先前比较了AIS与显示淋巴结转移或致命结果的eIA的表达谱，发现分层蛋白（SFN，14-3-3 sigma）是与细胞增殖相关的差异表达基因。在这里，我们进行了一项体内研究，以澄清SFN在肺腺癌的发生和发展中的作用。通过siSFN抑制A549（人肺腺癌细胞系）中的SFN表达显著降低细胞增殖活性和S期亚群。在体内，shSFN转染的A549细胞中的肿瘤发展或转移到肺中减少。此外，我们产生了SFN转基因小鼠（Tg-SPC-SFN+/−），其显示在组织特异性增强子SPC启动子的控制下肺特异性表达人SFN。我们发现，在给予化学致癌物NNK后，Tg-SPC-SFN+/−小鼠的肺肿瘤发生率显著高于对照小鼠。有趣的是，几只Tg-SPC-SFN+/−小鼠在没有NNK的情况下发生了肿瘤。这些肿瘤细胞显示高hSFN表达。这些结果表明，SFN促进肺肿瘤的发展和进展。SFN似乎是一种新的癌基因，具有作为治疗靶点的潜力。本文的在线版本（doi：10.1186/s12943-015-0414-1）包含补充材料，可供授权用户使用。
Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis. However, early but invasive adenocarcinoma (eIA) sometimes has a fatal outcome. We had previously compared the expression profiles of AIS with those of eIA showing lymph node metastasis or a fatal outcome, and found that stratifin (SFN, 14-3-3 sigma) was a differentially expressed gene related to cell proliferation. Here, we performed an in vivo study to clarify the role of SFN in initiation and progression of lung adenocarcinoma. Suppression of SFN expression in A549 (a human lung adenocarcinoma cell line) by siSFN significantly reduced cell proliferation activity and the S-phase subpopulation. In vivo, tumor development or metastasis to the lung was reduced in shSFN-transfected A549 cells. Moreover, we generated SFN-transgenic mice (Tg-SPC-SFN+/−) showing lung-specific expression of human SFN under the control of a tissue-specific enhancer, the SPC promoter. We found that Tg-SPC-SFN+/− mice developed lung tumors at a significantly higher rate than control mice after administration of chemical carcinogen, NNK. Interestingly, several Tg-SPC-SFN+/− mice developed tumors without NNK. These tumor cells showed high hSFN expression. These results suggest that SFN facilitates lung tumor development and progression. SFN appears to be a novel oncogene with potential as a therapeutic target. The online version of this article (doi:10.1186/s12943-015-0414-1) contains supplementary material, which is available to authorized users.