Estrogen suppresses HOXB2 expression via ERα in breast cancer cells.
Animals
Breast Neoplasms
/ genetics
Cell Line, Tumor
Down-Regulation
Estrogen Receptor alpha
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Homeodomain Proteins
/ genetics
Humans
MCF-7 Cells
Mice
Neoplasm Transplantation
Phenols
/ administration & dosage
Promoter Regions, Genetic
Pyrazoles
/ administration & dosage
Transcription Factors
/ genetics
Breast cancer
Chromatin immunoprecipitation
Estrogen
Estrogen receptor α
Estrogen response elements
HOXB2
Journal
Gene
ISSN: 1879-0038
Titre abrégé: Gene
Pays: Netherlands
ID NLM: 7706761
Informations de publication
Date de publication:
20 Aug 2021
20 Aug 2021
Historique:
received:
28
08
2020
revised:
27
04
2021
accepted:
27
05
2021
pubmed:
2
6
2021
medline:
24
6
2021
entrez:
1
6
2021
Statut:
ppublish
Résumé
The expression of HOXB2, a homeobox transcription factor, is altered in a variety of solid tumors. Using an in vivo screen to identify regulators of breast tumor growth in murine mammary fat pads, Boimel and co-workers recently identified HOXB2 as a tumor suppressor. However, the mechanistic underpinnings of its role in breast cancer is not understood. Given the emerging interaction of estrogen-regulated gene expression and altered HOX gene expression network in the pathophysiology of breast cancer, this study addressed the relationship between estrogen signaling and HOXB2 expression. Using a mouse model and human breast cancer cell lines, we show that estrogen suppresses HOXB2 expression. Suppression of HOXB2 by PPT, a known ERα agonist, in MCF-7 and T47D cells indicated the involvement of ERα, which was confirmed by siRNA-mediated ERα knockdown experiments. In-silico analysis of the upstream promoter region revealed the presence of three putative EREs. Chromatin immunoprecipitation experiments showed that upon estrogen binding, ERα engaged with EREs in the 5' upstream region of HOXB2 in MCF-7 and T47D cells. Future investigations should address the implications of estrogen-mediated suppression on the proposed tumor suppressor function of HOXB2.
Identifiants
pubmed: 34062258
pii: S0378-1119(21)00340-1
doi: 10.1016/j.gene.2021.145746
pii:
doi:
Substances chimiques
ESR1 protein, human
0
Estrogen Receptor alpha
0
HOXB2 protein, human
0
Homeodomain Proteins
0
Phenols
0
Pyrazoles
0
Transcription Factors
0
4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
0T83Y6JZPF
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
145746Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.