瘦素通过激活人乳腺癌细胞中的 AP-1 来刺激 IGF-1 转录。
Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells.
机构信息
Department of Biological Sciences, Sanghuh College of Lifesciences, Koknkuk University, Seoul 05029, China.
Department of Biological Sciences, Sanghuh College of Lifesciences, Koknkuk University, Seoul 05029; Cancer and Metabolism Institute, Konkuk University, Seoul 05029, Korea.
出版信息
BMB Rep. 2019 Jun;52(6):385-390. doi: 10.5483/BMBRep.2019.52.6.189.
Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These results suggest that leptin contributes to breast cancer progression through the transcriptional upregulation of leptin via the MAPK pathway. [BMB Reports 2019; 52(6): 385-390].
瘦素是一种调节能量代谢的脂肪细胞因子，似乎与乳腺癌的进展有关。胰岛素样生长因子-1（IGF-1）介导乳腺癌的发病机制。瘦素对乳腺癌细胞中 IGF-1 表达的调节尚不清楚。在这里，我们发现瘦素在乳腺癌细胞中在上游区域的 IGF-1 启动子激活，上调 IGF-1 的转录水平。IGF-1 启动子激活所必需的转录因子激活蛋白-1（AP-1）结合元件。强制表达 AP-1 成分 c-FOS 或 c-JUN，增强了瘦素诱导的 IGF-1 表达，而 c-FOS 或 c-JUN 的敲低则消除了瘦素的反应性。所有三种 MAPK（ERK1/2、JNK1/2 和 p38 MAPK）介导瘦素诱导的 IGF-1 表达。这些结果表明，瘦素通过 MAPK 通路通过转录上调瘦素，从而促进乳腺癌的进展。[BMB 报告 2019;52(6):385-390]。
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