Open AccessLeptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells
Author(s) -
Dong Yeong Min,
Euitaek Jung,
Ju Hwan Kim,
Young Han Lee,
Soon Young Shin
Publication year - 2019
Publication title -
bmb reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.511
H-Index - 77
eISSN - 1976-670X
pISSN - 1976-6696
DOI - 10.5483/bmbrep.2019.52.6.189
Subject(s) - leptin , gene knockdown , endocrinology , breast cancer , medicine , adipokine , downregulation and upregulation , mapk/erk pathway , cancer research , cancer , transcription factor , leptin receptor , biology , signal transduction , microbiology and biotechnology , gene , obesity , biochemistry
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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