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...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7521 |
| _version_ | 1797446661943853056 |
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| author | Jin Hyung Kim Seung-Taek Lee |
| author_facet | Jin Hyung Kim Seung-Taek Lee |
| author_sort | Jin Hyung Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T13:44:45Z |
| format | Article |
| id | doaj.art-ee441e3f67cf4f84a09adc13c7147332 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:44:45Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ee441e3f67cf4f84a09adc13c71473322023-11-30T21:03:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314752110.3390/ijms23147521Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer CellsJin Hyung Kim0Seung-Taek Lee1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, KoreaPolyamine 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.https://www.mdpi.com/1422-0067/23/14/752117β-estradiol (E2)polyaminepolyamine oxidase (PAOX)estrogen receptor (ESR)activator protein 1 (AP-1) |
| spellingShingle | Jin Hyung Kim Seung-Taek Lee Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells International Journal of Molecular Sciences 17β-estradiol (E2) polyamine polyamine oxidase (PAOX) estrogen receptor (ESR) activator protein 1 (AP-1) |
| title | Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells |
| title_full | Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells |
| title_fullStr | Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells |
| title_full_unstemmed | Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells |
| title_short | Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells |
| title_sort | polyamine oxidase expression is downregulated by 17β estradiol via estrogen receptor 2 in human mcf 7 breast cancer cells |
| topic | 17β-estradiol (E2) polyamine polyamine oxidase (PAOX) estrogen receptor (ESR) activator protein 1 (AP-1) |
| url | https://www.mdpi.com/1422-0067/23/14/7521 |
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