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Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells
Dong Yeong Min1, Euitaek Jung1, Juhwan Kim1, Young Han Lee1,2, SoonYoung Shin1,2,*
1Biological Sciences and 2Cancer and Metabolism Institute, Koknkuk University
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.
Abstract, Accepted Manuscript(in press) [Submitted on August 17, 2018, Accepted on October 4, 2018]
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