Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells
Polyamine levels decrease with menopause; however, little is known about the mechanisms regulated by menopause. In this study, we found that among the genes involved in the polyamine pathway, polyamine oxidase (<i>PAOX</i>) mRNA levels were the most significantly reduced by treatment wit...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/14/7521 |
| Summary: | Polyamine levels decrease with menopause; however, little is known about the mechanisms regulated by menopause. In this study, we found that among the genes involved in the polyamine pathway, polyamine oxidase (<i>PAOX</i>) mRNA levels were the most significantly reduced by treatment with 17β-estradiol in estrogen receptor (ESR)-positive MCF-7 breast cancer cells. Treatment with 17β-estradiol also reduced the PAOX protein levels. Treatment with selective ESR antagonists and knockdown of ESR members revealed that estrogen receptor 2 (ESR2; also known as ERβ) was responsible for the repression of PAOX by 17β-estradiol. A luciferase reporter assay showed that 17β-estradiol downregulates <i>PAOX</i> promoter activity and that 17β-estradiol-dependent PAOX repression disappeared after deletions (−3126/−2730 and −1271/−1099 regions) or mutations of activator protein 1 (AP-1) binding sites in the <i>PAOX</i> promoter. Chromatin immunoprecipitation analysis showed that ESR2 interacts with AP-1 bound to each of the two AP-1 binding sites. These results demonstrate that 17β-estradiol represses <i>PAOX</i> transcription by the interaction of ESR2 with AP-1 bound to the <i>PAOX</i> promoter. This suggests that estrogen deficiency may upregulate PAOX expression and decrease polyamine levels. |
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| ISSN: | 1661-6596 1422-0067 |