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
TLDR 17β-estradiol lowers polyamine oxidase levels in breast cancer cells through estrogen receptor 2.
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.
