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Suppression of estrogen receptor transcriptional activity by connective tissue growth factor.

Cheng L, Yang Z, Wang X, Jiao Y, Xie X, Lin J, Zhang H, Han J, Jiang K, Ye Q - PLoS ONE (2011)

Bottom Line: Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity.The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF.Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.

ABSTRACT
Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER) that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF) physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs.

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Related in: MedlinePlus

CTGF reduces estrogen-responsive protein expression.MCF7 cells stably transfected with FLAG-tagged CTGF were treated with E2 or without E2. Conditioned media were blotted with antibodies to cathepsin D (CatD), pS2 and FLAG, and whole cell lysates were blotted with anti-GAPDH.
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pone-0020028-g005: CTGF reduces estrogen-responsive protein expression.MCF7 cells stably transfected with FLAG-tagged CTGF were treated with E2 or without E2. Conditioned media were blotted with antibodies to cathepsin D (CatD), pS2 and FLAG, and whole cell lysates were blotted with anti-GAPDH.

Mentions: To corroborate the results of the luciferase reporter assays, the effect of CTGF on the expression of endogenous estrogen-responsive genes was examined. The E2-deprived MCF-7 cells stably expressing either the empty vector or FLAG-tagged CTGF were treated with 10 nM E2 for 20 h. As expected, E2 increased the expression of two well-studied estrogen-responsive genes [3], pS2 and cathepsin D, in the empty vector-transfected cells (Fig. 5). Importantly, the transfection of CTGF decreased the expression of pS2 and cathepsin D both in the absence and in the presence of E2. These data suggest that CTGF represses the expression of endogenous ERα-responsive genes.


Suppression of estrogen receptor transcriptional activity by connective tissue growth factor.

Cheng L, Yang Z, Wang X, Jiao Y, Xie X, Lin J, Zhang H, Han J, Jiang K, Ye Q - PLoS ONE (2011)

CTGF reduces estrogen-responsive protein expression.MCF7 cells stably transfected with FLAG-tagged CTGF were treated with E2 or without E2. Conditioned media were blotted with antibodies to cathepsin D (CatD), pS2 and FLAG, and whole cell lysates were blotted with anti-GAPDH.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101213&req=5

pone-0020028-g005: CTGF reduces estrogen-responsive protein expression.MCF7 cells stably transfected with FLAG-tagged CTGF were treated with E2 or without E2. Conditioned media were blotted with antibodies to cathepsin D (CatD), pS2 and FLAG, and whole cell lysates were blotted with anti-GAPDH.
Mentions: To corroborate the results of the luciferase reporter assays, the effect of CTGF on the expression of endogenous estrogen-responsive genes was examined. The E2-deprived MCF-7 cells stably expressing either the empty vector or FLAG-tagged CTGF were treated with 10 nM E2 for 20 h. As expected, E2 increased the expression of two well-studied estrogen-responsive genes [3], pS2 and cathepsin D, in the empty vector-transfected cells (Fig. 5). Importantly, the transfection of CTGF decreased the expression of pS2 and cathepsin D both in the absence and in the presence of E2. These data suggest that CTGF represses the expression of endogenous ERα-responsive genes.

Bottom Line: Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity.The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF.Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.

ABSTRACT
Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER) that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF) physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs.

Show MeSH
Related in: MedlinePlus