Pten in stromal fibroblasts suppresses mammary epithelial tumours.
Pten in stromal fibroblasts suppresses mammary epithelial tumours.
复制标题
作者：
肿瘤间质被认为有助于上皮肿瘤的一些最恶性的特征。然而，间质细胞和肿瘤细胞之间的信号传导是复杂的，并且仍然知之甚少。在这里，我们表明，基因失活的Pten在小鼠乳腺间质成纤维细胞加速乳腺上皮性肿瘤的发生，发展和恶性转化。这与细胞外基质（ECM）的大量重塑、先天免疫细胞浸润和血管生成增加有关。基质成纤维细胞中Pten的缺失导致Ets 2的表达、磷酸化（T72）和募集增加，以靶向已知参与这些过程的启动子。值得注意的是，Pten基质缺失肿瘤中的Ets 2失活改善了肿瘤微环境的破坏，足以降低肿瘤的生长和进展。乳腺间质细胞的全局基因表达谱鉴定了在乳腺癌患者的肿瘤间质中高度代表的Pten特异性签名。这些发现将Pten-Ets 2轴确定为抑制乳腺上皮肿瘤的关键基质特异性信号通路。
The tumor stroma is believed to contribute to some of the most malignant characteristics of epithelial tumors. However, signaling between stromal and tumor cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumors. This was associated with the massive remodeling of the extra-cellular matrix (ECM), innate immune cell infiltration and increased angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression, phosphorylation (T72) and recruitment of Ets2 to target promoters known to be involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted tumors ameliorated disruption of the tumor microenvironment and was sufficient to decrease tumor growth and progression. Global gene expression profiling of mammary stromal cells identified a Pten-specific signature that was highly represented in the tumor stroma of breast cancer patients. These findings identify the Pten-Ets2 axis as a critical stroma-specific signaling pathway that suppresses mammary epithelial tumors.
登录
查看更多内容
DOI：
10.1083/jcb.200409115
发表时间：
2005-05-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lee S;Jilani SM;Nikolova GV;Carpizo D;Iruela-Arispe ML
通讯作者：
Iruela-Arispe ML
影响因子：
5.3
作者：
McCarthy, SA;Chen, D;McMahon, M
通讯作者：
McMahon, M
影响因子：
5.3
作者：
Hu, Rong;Sharma, Sudarshana M.;Ostrowski, Michael C.
通讯作者：
Ostrowski, Michael C.
影响因子：
5.3
作者：
Fowles, LF;Martin, ML;Ostrowski, MC
通讯作者：
Ostrowski, MC
影响因子：
7.3
作者：
Bergamaschi, A.;Tagliabue, E.;Borresen-Dale, A-L
通讯作者：
Borresen-Dale, A-L