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Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells

  • Min, Dong Yeong (Department of Biological Sciences, Sanghuh College of Lifesciences, Koknkuk University) ;
  • Jung, Euitaek (Department of Biological Sciences, Sanghuh College of Lifesciences, Koknkuk University) ;
  • Kim, Juhwan (Department of Biological Sciences, Sanghuh College of Lifesciences, Koknkuk University) ;
  • Lee, Young Han (Department of Biological Sciences, Sanghuh College of Lifesciences, Koknkuk University) ;
  • Shin, Soon Young (Department of Biological Sciences, Sanghuh College of Lifesciences, Koknkuk University)
  • Received : 2018.08.17
  • Accepted : 2018.10.04
  • Published : 2019.06.30

Abstract

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.

Keywords

References

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