Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic.
Cancer Lett. 2013 Jun 10;333(2):187-93. doi: 10.1016/j.canlet.2013.01.034. Epub 2013 Jan 24.
The pro-metastatic protein anterior gradient-2 (AGR2) was previously demonstrated as a predictive factor of poor response to tamoxifen treatment. In this study we aimed to delineate the key signalling pathway that may contribute to regulation of AGR2 protein induction in order to identify novel targets to overcome tamoxifen resistance in tumour cells. Together, our data identify PDPK1-AKT as a pro-oncogenic signalling pathway that triggers AGR2 protein induction in response to tamoxifen and suggest that AKT inhibitors could be used as part of a therapeutic strategy to treat tamoxifen resistant, AGR2 over-expressing cancers.
先前的研究表明，促转移蛋白前梯度-2（AGR2）是对他莫昔芬治疗反应不良的预测因子。在这项研究中，我们旨在描绘可能有助于调节 AGR2 蛋白诱导的关键信号通路，以确定克服肿瘤细胞中他莫昔芬耐药性的新靶标。我们的数据共同确定 PDPK1-AKT 作为一种致癌信号通路，该通路触发 AGR2 蛋白在他莫昔芬作用下的诱导，并表明 AKT 抑制剂可用作治疗他莫昔芬耐药、AGR2 过表达癌症的治疗策略的一部分。
