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Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells
In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflamm...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865376/ https://www.ncbi.nlm.nih.gov/pubmed/36674737 http://dx.doi.org/10.3390/ijms24021221 |
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author | Diaz-Ruano, Ana Belén Martinez-Alarcon, Nuria Perán, Macarena Benabdellah, Karim Garcia-Martinez, María de los Ángeles Preda, Ovidiu Ramirez-Tortosa, César Gonzalez-Hernandez, Andrea Marchal, Juan Antonio Picon-Ruiz, Manuel |
author_facet | Diaz-Ruano, Ana Belén Martinez-Alarcon, Nuria Perán, Macarena Benabdellah, Karim Garcia-Martinez, María de los Ángeles Preda, Ovidiu Ramirez-Tortosa, César Gonzalez-Hernandez, Andrea Marchal, Juan Antonio Picon-Ruiz, Manuel |
author_sort | Diaz-Ruano, Ana Belén |
collection | PubMed |
description | In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-to-mesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17β-Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases. |
format | Online Article Text |
id | pubmed-9865376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98653762023-01-22 Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells Diaz-Ruano, Ana Belén Martinez-Alarcon, Nuria Perán, Macarena Benabdellah, Karim Garcia-Martinez, María de los Ángeles Preda, Ovidiu Ramirez-Tortosa, César Gonzalez-Hernandez, Andrea Marchal, Juan Antonio Picon-Ruiz, Manuel Int J Mol Sci Article In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-to-mesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17β-Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases. MDPI 2023-01-07 /pmc/articles/PMC9865376/ /pubmed/36674737 http://dx.doi.org/10.3390/ijms24021221 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Diaz-Ruano, Ana Belén Martinez-Alarcon, Nuria Perán, Macarena Benabdellah, Karim Garcia-Martinez, María de los Ángeles Preda, Ovidiu Ramirez-Tortosa, César Gonzalez-Hernandez, Andrea Marchal, Juan Antonio Picon-Ruiz, Manuel Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells |
title | Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells |
title_full | Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells |
title_fullStr | Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells |
title_full_unstemmed | Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells |
title_short | Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells |
title_sort | estradiol and estrone have different biological functions to induce nf-κb-driven inflammation, emt and stemness in er+ cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865376/ https://www.ncbi.nlm.nih.gov/pubmed/36674737 http://dx.doi.org/10.3390/ijms24021221 |
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