Characterization of ERα Signaling to Cell Proliferation Induced by Chronic and Pulsatile E2 Stimulation in 2D and 3D Cell Cultures.
17β‐estradiol
alginate spheres
breast cancer
estrogen receptor
three‐dimensional cell cultures
Journal
Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768
Informations de publication
Date de publication:
11 Jun 2024
11 Jun 2024
Historique:
revised:
19
03
2024
received:
13
10
2023
accepted:
24
05
2024
medline:
11
6
2024
pubmed:
11
6
2024
entrez:
11
6
2024
Statut:
aheadofprint
Résumé
17β-estradiol is a hormone that plays a vital role in human physiology. It acts through estrogen receptors, specifically estrogen receptor α and estrogen receptor β, and its action is determined by the pulsatile secretion in the bloodstream. 17β-estradiol affects cell proliferation, and dysregulation of 17β-estradiol:estrogen receptor α signaling contribute to the development of breast cancer. Previous research on 17β-estradiol:estrogen receptor α signaling has primarily used two-dimensional cell cultures, which do not fully recapitulate the complexity of tumors that exist in a three-dimensional environment and do not consider the pulsatile nature of this hormone. To address these limitations, we studied 17β-estradiol:estrogen receptor α signaling in cell proliferation using both two-dimensional and three-dimensional breast cancer cell culture models under continuous and pulsatile stimulation conditions. Results revealed that breast cancer cells grown in an alginate-based three-dimensional matrix exhibited similar responsiveness to 17β-estradiol compared with cells grown in conventional two-dimensional culture plates. 17β-estradiol induced the expression of proteins containing estrogen response element in the three-dimensional model. The efficacy of the antiestrogen drugs fulvestrant (ICI182,280) and 4OH-tamoxifen was also demonstrated in the three-dimensional model. These results support the use of the three-dimensional culture model for studying tumor response to drugs and provide a more realistic microenvironment for such studies. Furthermore, the study revealed that a brief 5-min exposure to 17β-estradiol triggered a physiological response comparable with continuous hormone exposure, suggesting that the cellular response to 17β-estradiol is more important than the continuous presence of the hormone. In conclusion, the study demonstrates that the alginate-based three-dimensional culture model is suitable for studying the effects of 17β-estradiol and antiestrogen drugs on breast cancer cells, offering a more realistic representation of tumor-microenvironment interactions. The results also highlight the importance of considering the physiological importance of the temporal dynamics in studying 17β-estradiol signaling and cellular responses.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e30610Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 2018 - ID. 21325 project
Organisme : Ministero della Salute
ID : RF-2021-12372851
Organisme : Ministero della Salute
ID : CUPF83C22002620001
Organisme : The Grant of Excellence Departments 2023-2027
ID : MIUR (ARTICOLO 1, COMMI 314-337 LEGGE 232/2016).
Informations de copyright
© 2024 Wiley Periodicals LLC.
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