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cJUN NH-末端激酶（JNK）信号通路促进基因组稳定性并防止肿瘤起始。

The cJUN NH-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation.

机构信息

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.

Histo-Scientific Research Laboratories, Mount Jackson, United States.

出版信息

Elife. 2018 Jun 1;7:e36389. doi: 10.7554/eLife.36389.

DOI:10.7554/eLife.36389
PMID:29856313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5984035/
Abstract

Breast cancer is the most commonly diagnosed malignancy in women. Analysis of breast cancer genomic DNA indicates frequent mutations in components of the cJUN NH-terminal kinase (JNK) signaling pathway. Since JNK signaling can promote cell proliferation by activating the AP1 transcription factor, this apparent association of reduced JNK signaling with tumor development was unexpected. We examined the effect of JNK deficiency in the murine breast epithelium. Loss of JNK signaling caused genomic instability and the development of breast cancer. Moreover, JNK deficiency caused widespread early neoplasia and rapid tumor formation in a murine model of breast cancer. This tumor suppressive function was not mediated by a role of JNK in the growth of established tumors, but by a requirement of JNK to prevent tumor initiation. Together, these data identify JNK pathway defects as 'driver' mutations that promote genome instability and tumor initiation.

摘要

乳腺癌是女性最常见的恶性肿瘤。对乳腺癌基因组 DNA 的分析表明，cJUN NH-末端激酶（JNK）信号通路的组成部分经常发生突变。由于 JNK 信号可以通过激活 AP1 转录因子促进细胞增殖，因此这种与肿瘤发展相关的 JNK 信号减弱的明显关联是出乎意料的。我们研究了 JNK 缺乏对小鼠乳腺上皮的影响。JNK 信号的丧失导致基因组不稳定和乳腺癌的发生。此外，JNK 缺乏导致在乳腺癌的小鼠模型中广泛出现早期肿瘤和快速肿瘤形成。这种肿瘤抑制功能不是通过 JNK 在已建立的肿瘤生长中的作用来介导的，而是通过 JNK 预防肿瘤起始的需要来介导的。总之，这些数据表明 JNK 通路缺陷是促进基因组不稳定和肿瘤起始的“驱动”突变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d6/5984035/3341fd1529ba/elife-36389-resp-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d6/5984035/6cdae9a49e37/elife-36389-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d6/5984035/805132e54d13/elife-36389-fig1-figsupp1.jpg
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3
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4
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