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Fli1 Is a Negative Regulator of Estrogen Receptor α in Dermal Fibroblasts.
- Source :
-
Journal of Investigative Dermatology . Jul2011, Vol. 131 Issue 7, p1469-1476. 8p. - Publication Year :
- 2011
-
Abstract
- Estrogen is an important regulator of dermal fibroblast functions, including extracellular matrix (ECM) synthesis. Estrogen mediates its effects through estrogen receptors (ERs), ERα and ERβ; however, regulation of ERs in dermal fibroblasts remains poorly understood. Friend leukemia integration factor 1 (Fli1), a member of the Ets transcription factor family, has been shown to play a pivotal role in regulation of the ECM genes in dermal fibroblasts. The aim of this study was to examine a possible interaction between Fli1 and estrogen pathways, focusing on ERα. We show that treatment of human dermal fibroblasts with transforming growth factor-β (TGF-β) increases ERα protein and mRNA levels. Similarly, ERα expression was increased in response to small interfering RNA (siRNA)-mediated depletion of Fli1, suggesting that Fli1 is a mediator of the TGF-β effects on ERα expression. Accordingly, we showed that Fli1 binds to the most proximal region of the ERα promoter, and dissociates from the promoter upon TGF-β treatment. An inverse correlation between Fli1 and ERα expression levels was confirmed in cultured skin fibroblasts obtained from Fli1+/- mice and in the skin of Fli1+/- mice in vivo. This study supports a role of Fli1 as a negative regulator of the ERα gene in dermal fibroblasts. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ESTROGEN
*FIBROBLASTS
*EXTRACELLULAR matrix
*LEUKEMIA
*GENES
Subjects
Details
- Language :
- English
- ISSN :
- 0022202X
- Volume :
- 131
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Journal of Investigative Dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 61249153
- Full Text :
- https://doi.org/10.1038/jid.2011.63