Estradiol and Estrone Have Different Biological Functions to Induce NF-kappa B-Driven Inflammation, EMT and Stemness in ER plus Cancer Cells
Metadatos
Afficher la notice complèteAuteur
Díaz Ruano, Ana Belén; Martínez Alarcón, Nuria; Perán, Macarena; Benabdellah, Karim; García Martínez, María de los Ángeles; Preda, Ovidiu; Ramírez Tortosa, César Luis; González hernández, Andrea; Marchal Corrales, Juan Antonio; Picón Ruiz, ManuelEditorial
MDPI
Materia
ER+ cancer Estradiol Estrone Inflammation NF-KB HSD17B
Date
2023-01-07Referencia bibliográfica
Diaz-Ruano, A.B... [et al.]. Estradiol and Estrone Have Different Biological Functions to Induce NF- B-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells. Int. J. Mol. Sci. 2023, 24, 1221. [https://doi.org/10.3390/ijms24021221]
Patrocinador
Instituto de Salud Carlos III PIE16-00045; Ministry of Health and Family of the Junta de Andalucia; European Commission PEMP-0205-2020; Spanish Ministry of Science, Innovation and Universities (MICIN) MSCA-IF-2018 845104; European Commission European Commission Joint Research Centre PID2020-119502RJ-I00; State Research Agency from the Spanish Ministry of Science and Innovation (MICIN/AEI) CMC-CTS963 0006/2018; Chair "Doctors Galera-Requena in cancer stem cell research" PECART-0027-2020 regional Ministry of Health; Consejeria de Salud y Familias RTI2018-101309-B-C22 RYC2020-030808-IRésumé
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-tomesenchymal
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 17 -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.