Leptin is a direct transcriptional target of EGR1 in human breast cancer cells

Mol Biol Rep. 2019 Feb;46(1):317-324. doi: 10.1007/s11033-018-4474-3. Epub 2018 Nov 11.

Abstract

Leptin is a cytokine that regulates energy metabolism. Leptin can promote breast cancer progression in obese women. However, the mechanism of regulation of leptin expression in breast cancer cells is unclear. Tumor necrosis factor-alpha (TNF-α) stimulated the transcription of the leptin gene. Using mutant promoter constructs, we demonstrated that the EGR1-binding motif in the proximal region of the leptin gene is required for leptin transcription by TNF-α. Forced expression of EGR1 stimulated leptin promoter activity, whereas silencing of EGR1 by RNA interference reduced TNF-α-induced leptin protein accumulation. The ERK1/2 pathway contributed to the expression of EGR1 and leptin by TNF-α. Our results suggest that EGR1 targets the leptin gene in response to TNF-α stimulation in breast cancer cells.

Keywords: Breast cancer; EGR1; ERK1/2; Leptin; Tissue necrosis factor alpha.

MeSH terms

  • Binding Sites
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Leptin / genetics
  • Leptin / physiology*
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Transcription, Genetic / drug effects
  • Transcriptional Activation / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Leptin
  • RNA, Messenger
  • Transcription Factors
  • Tumor Necrosis Factor-alpha