Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells
July 2022
in “
International Journal of Molecular Sciences
”
17β-estradiol estrogen receptor 2 polyamine oxidase PAOX MCF-7 breast cancer cells estrogen receptor-positive mRNA protein levels ESR2 selective ESR antagonists knockdown luciferase reporter assay promoter activity activator protein 1 AP-1 chromatin immunoprecipitation transcription estrogen deficiency estrogen ER2 breast cancer cells protein estrogen receptor antagonists gene knockdown reporter assay gene promoter gene transcription hormone deficiency
The study investigated the effect of 17β-estradiol on polyamine oxidase (PAOX) expression in estrogen receptor-positive MCF-7 breast cancer cells. It was found that 17β-estradiol significantly reduced both PAOX mRNA and protein levels. The repression of PAOX was mediated by estrogen receptor 2 (ESR2), as shown by experiments using selective ESR antagonists and knockdown of ESR members. A luciferase reporter assay indicated that 17β-estradiol downregulated PAOX promoter activity, and this effect was lost when specific activator protein 1 (AP-1) binding sites in the PAOX promoter were deleted or mutated. Chromatin immunoprecipitation analysis confirmed that ESR2 interacts with AP-1 at these sites. The findings suggested that 17β-estradiol represses PAOX transcription through ESR2's interaction with AP-1, implying that estrogen deficiency could lead to increased PAOX expression and decreased polyamine levels.
