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. [BMB Reports 2019; 52(6): 385-390].
MeSH terms
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Disease Progression
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Female
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Humans
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Insulin-Like Growth Factor I / biosynthesis
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism*
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Leptin / metabolism
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Leptin / pharmacology*
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MCF-7 Cells
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Mitogen-Activated Protein Kinase 3 / metabolism
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Promoter Regions, Genetic
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Proto-Oncogene Proteins c-fos / metabolism
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Proto-Oncogene Proteins c-jun / metabolism
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Signal Transduction / drug effects
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism*
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Transcriptional Activation / drug effects
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Up-Regulation / drug effects
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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IGF1 protein, human
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LEP protein, human
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Leptin
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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Transcription Factor AP-1
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Insulin-Like Growth Factor I
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases