Estradiol regulates Tumor Necrosis Factor-α expression and secretion in Estrogen Receptor positive breast cancer cells.
Mol Cell Endocrinol
; 394(1-2): 21-8, 2014 Aug 25.
Article
in En
| MEDLINE
| ID: mdl-25004254
ABSTRACT
The cytokine Tumor Necrosis Factor-α is critical to Estrogen Receptor positive breast cancer pathology, stimulating estrogen-biosynthesis pathways and preventing the differentiation of estrogen-producing fibroblasts. High concentrations of TNFα are detected in the tumor microenvironment, and infiltrating immune cells are thought to be a major source. This study identifies that TNFα is also a tumor-derived factor, expressed in ER+ tumour epithelial cells and regulated by 17-ß-estradiol (E2). Treatment of MCF-7, T47D and ZR-75 breast cancer cells with E2 increased TNFα mRNA and protein expression and secretion. This effect was mitigated with the use of ERα inhibitors 4-hydroy-tamoxifen and ICI-182780, indicating that E2-mediated TNFα induction was via the actions of ERα. Chromatin immunoprecipitation reveals ERα binding to the TNFα promoter upon stimulation with E2. This study demonstrates for the first time a positive feedback loop between estradiol and TNFα, critical in maintaining high levels of the hormone within the ER+ breast tumour microenvironment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Gene Expression Regulation, Neoplastic
/
Tumor Necrosis Factor-alpha
/
Estrogen Receptor alpha
/
Epithelial Cells
/
Estradiol
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Cell Endocrinol
Year:
2014
Document type:
Article
Affiliation country:
Australia