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

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].

SUBMITTER: Min DY

PROVIDER: S-EPMC6605521 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Min Dong Yeong DY Jung Euitaek E Kim Juhwan J Lee Young Han YH Shin Soon Young SY

BMB reports 20190601 6

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 pro ...[more]

PMID: 30293548

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