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KMID : 0624620190520060385
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BMB Reports
2019 Volume.52 No. 6 p.385 ~ p.390
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Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells
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Min Dong-Yeong
Jung Eui-Taek
Kim Ju-Hwan
Lee Young-Han
Shin Soon-Young
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Abstract
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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.
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KEYWORD
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Activating protein-1, Breast cancer, Insulin-like growth factor-1, Leptin, Mitogen-activated protein kinase
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