17-β-estradiol inhibits transforming-growth-factor-β-induced MCF-7 cell migration by Smad3-repression

Malek, Daniela; Gust, Ronald; Kleuser, Burkhard

doi:10.1016/j.ejphar.2006.01.025

Cited by 34 publications

(31 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In MCF-7 cells, TGF-␤-induced transcription and migratory potential are inhibited by estrogen (31), and activin and estrogen signaling are reciprocally suppressed their signaling (32). Smad3-dependent transcription is inhibited by ER␣ through binding to Smad3, and the inhibition is abrogated by the expression of AP-1 transcription factors (33,34).…”

mentioning

confidence: 99%

Estrogen Inhibits Transforming Growth Factor β Signaling by Promoting Smad2/3 Degradation

Ito

Hanyu

Wayama

et al. 2010

Journal of Biological Chemistry

143

112

View full text Add to dashboard Cite

Estrogen is a growth factor that stimulates cell proliferation. The effects of estrogen are mediated through the estrogen receptors, ER␣ and ER␤, which function as ligand-induced transcription factors and belong to the nuclear receptor superfamily. On the other hand, TGF-␤ acts as a cell growth inhibitor, and its signaling is transduced by Smads. Although a number of studies have been made on the cross-talk between estrogen/ER␣ and TGF-␤/Smad signaling, whose molecular mechanisms remain to be determined. Here, we show that ER␣ inhibits TGF-␤ signaling by decreasing Smad protein levels. ER␣-mediated reductions in Smad levels did not require the DNA binding ability of ER␣, implying that ER␣ opposes the effects of TGF-␤ via a novel non-genomic mechanism. Our analysis revealed that ER␣ formed a protein complex with Smad and the ubiquitin ligase Smurf, and enhanced Smad ubiquitination and subsequent degradation in an estrogen-dependent manner. Our observations provide new insight into the molecular mechanisms governing the non-genomic functions of ER␣.

show abstract

mentioning

confidence: 99%

Estrogen Inhibits Transforming Growth Factor β Signaling by Promoting Smad2/3 Degradation

Ito

Hanyu

Wayama

et al. 2010

Journal of Biological Chemistry

143

112

View full text Add to dashboard Cite

show abstract

“…This is depicted in Figure 1A. Further studies showed that E 2 blocked Smad 3 activation in both MCF-7 and renal mesangial cells [Malek et al, 2006]. However, estrogen treatment of OBs actually enhances Smad-dependent gene expression in response to TGFβ [McCarthy et al, 2003].…”

Section: Levels 3 and 4 Cross-talk: The Er-smad Interaction And Altermentioning

confidence: 96%

“…However, estrogen treatment of OBs actually enhances Smad-dependent gene expression in response to TGFβ [McCarthy et al, 2003]. In contrast, TGFβ treatment (i.e., Smad activation) is known to enhance the E 2 -induced ERE reporter gene activity in multiple cell types [Malek et al, 2006]. Other studies implicate a role for Smad 4-ERα interactions [Wu et al, 2003;Li et al, 2005].…”

mentioning

confidence: 90%

“…Since Runx2 has been shown to interact not only with TIEG, but also with Smads 2/3 [Zhang et al, 2000] and ER [Matsuda et al, 2001;McCarthy et al, 2003], we have included the TIEG-Runx2, TIEG-ER, and TIEGSmad heterodimers in this figure. The Smad-Runx2 complex reduces Runx2 activity in OBs [Janssens et al, 2005;Malek et al, 2006] while the ER-Runx2 complex reportedly enhances the TGFβ/Smad signaling pathway in these cells [Matsuda et al, 2001;McCarthy et al, 2003]. The exact action of the TIEG-Runx2 heterodimers is currently under study.…”

Section: Role Of Tieg In the E 2 /Tgfβ Induction Of Runx2mentioning

confidence: 99%

See 1 more Smart Citation

Estrogen‐TGFβ cross‐talk in bone and other cell types: Role of TIEG, Runx2, and other transcription factors

Hawse

Subramaniam

Ingle

et al. 2007

J of Cellular Biochemistry

View full text Add to dashboard Cite

It is well established that E 2 and TGFβ have major biological effects in multiple tissues, including bone. The signaling pathways through which these two factors elicit their effects are well documented. However, the interaction between these two pathways and the potential consequences of cross-talk between E 2 and TGFβ continue to be elucidated. In this prospectus, we present known and potential roles of TIEG, Runx2, and other transcription factors as important mediators of signaling between these two pathways. KeywordsBone; Runx2; TIEG; Estrogen; TGFβ; osteoblast; osteoclast Estrogen (E 2 ) and TGFβ are known to be major regulators of skeletal formation and maintenance Spelsberg et al., 1999;Rickard et al., 2002a;Janssens et al., 2005]. In the past there have been numerous reports about the interaction (cross-talk) between these two important regulators, many of which involve transcription factors. This prospectus summarizes some of these studies and proposes some potential areas of crosstalk in osteoblast (OB) cells which includes Runx2 and another important factor discovered by our laboratory, the TGFβ inducible early gene-1 (TIEG), also known as Krüppel-like transcription factor-10 (KLF-10) [Subramaniam et al., 1995]. ESTROGEN ACTION IN OB CELLSThe skeleton is one of the main targets of E 2 action in the body as it regulates bone growth and remodeling. Estrogen has major effects on OB and osteoclast (OC) differentiation, including OB proliferation, differentiation, matrix production, and mineralization [Hughes et al., 1996;Robinson and Spelsberg, 1997;Oursler, 1998;Khosla et al., 1999;Rickard et al., 1999Rickard et al., , 2002aSpelsberg et al., 1999]. Decreased E 2 levels are known to be one of the main causes of osteoporosis [Melton, 1995;Gallagher, 1996] and there is abundant evidence demonstrating a critical role for E 2 in regulating bone metabolism and homeostasis in both [Riggs et al., 2002]. It is important to understand E 2 action in the skeleton to better define the mechanisms of bone loss and in order to develop new approaches to prevent and treat osteoporosis. The primary mechanism by which E 2 elicits its effects on target tissues is by binding to, and activating, the two major estrogen receptor (ER) isoforms, ERα and ERβ. It was originally believed that ERβ only modulated the activity of ERα; however, recent studies by our laboratory and others have demonstrated that these two receptors regulate distinct sets of genes in OBs [Waters et al., 2001;Rickard et al., 2002b;Monroe et al., 2003a;Kian Tee et al., 2004;Stossi et al., 2004;Monroe et al., 2005]. Adding to this complexity is the identification of a host of nuclear receptor co-activators and corepressors that modulate E 2 action [McKenna et al., 1999]. OBs express both ERα and ERβ, and both are differentially expressed during OB maturation. The ERα concentrations in rat OB cells increase by almost 10-fold during the differentiation of OB precursor cells into mature OBs, whereas ERβ concentrations increase only slightly, but remain ...

show abstract

“…Malek [92,93,94] showed that comparable to E2, the pure anti-estrogen faslodex, which has been proved to bind to GPR30 in an agonistic manner, impaired migration and Smad phosphorylation in response to transforming growth factor (TGF)-b through a pertussis toxin-(PTX-) sensitive mechanism. Concrete evidence for GPR30 as a mediator of E2-induced interruption of TGF-b signalling could successfully be provided by transfection experiments.…”

Section: Estrogen Receptor Transcriptionmentioning

confidence: 99%

Breast Cancer, Estrogen Receptor and Ligands

Bai

Gust²

2009

Archiv der Pharmazie

Self Cite

114

View full text Add to dashboard Cite

This review emphasizes the relationship of breast cancer, estrogen receptor and ligands, especially the centrality of the estrogen receptor, which mediates on one hand the hormone-induced gene transcription and on the other hand the anti-estrogen action against breast cancer. The characterization of the estrogen receptor ligand-binding domain co-crystallized with agonists or antagonists provided a molecular basis to gain an insight into the regulation of estrogen receptor and, thereby, to describe the mechanism of the hormone therapy in treating breast cancer.

show abstract

17-β-estradiol inhibits transforming-growth-factor-β-induced MCF-7 cell migration by Smad3-repression

Cited by 34 publications

References 41 publications

Estrogen Inhibits Transforming Growth Factor β Signaling by Promoting Smad2/3 Degradation

Estrogen Inhibits Transforming Growth Factor β Signaling by Promoting Smad2/3 Degradation

Estrogen‐TGFβ cross‐talk in bone and other cell types: Role of TIEG, Runx2, and other transcription factors

Breast Cancer, Estrogen Receptor and Ligands

Contact Info

Product

Resources

About