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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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