17β-Estradiol signaling in skeletal muscle cells and its relationship to apoptosis

Boland, Ricardo; Vasconsuelo, Andrea Anahi; Milanesi, Lorena Magdalena; Ronda, Ana Carolina; Boland, Ana Russo de

doi:10.1016/j.steroids.2007.12.027

Cited by 54 publications

(39 citation statements)

References 18 publications

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“…The estrogen receptors mediate the effect of estrogen under physiological and pathological conditions either by activation of estrogen target genes transcription by binding to specific estrogen response elements (42) or via nongenomic mechanisms which results in the rapid activation of several signal transduction pathways to regulate different cellular processes, such as proliferation, apoptosis, and differentiation. Estrogen exerts a proliferative effect via non-genomic activation of ERK1/2 and PI3K/AKT (43). To determine whether overexpressed Mig-6 regulate ERK1/2 phosphorylation in PTEN-null endometrial cancer, we assessed the expression of phospho-ERK1/2 by immunohistochemistry and Western blot.…”

Section: Discussionmentioning

confidence: 99%

Mig-6 Suppresses Endometrial Cancer Associated with Pten Deficiency and ERK Activation

et al. 2014

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PTEN mutations are the most common genetic alterations in endometrial cancer. Loss of PTEN and subsequent AKT activation stimulate ERα-dependent pathways that play an important role in endometrial tumorigenesis. The major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid hormone control over uterine epithelial cell proliferation and apoptosis. However, the precise mechanism of PTEN/AKT signaling in endometrial cancer remains poorly understood. The progesterone signaling mediator MIG-6 suppresses estrogen signaling and it has been implicated previously as a tumor suppressor in endometrial cancer. In this study, we show that MIG-6 also acts as a tumor suppressor in endometrial cancers associated with PTEN deficiency. Transgenic mice where Mig-6 was overexpressed in PR-expressing cells exhibited a relative reduction in uterine tumorigenesis caused by Pten deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an ERK1/2 inhibitor suppressed cancer progression in PRcre/+Ptenf/f mice. In clinical specimens of endometrial cancer, MIG-6 expression correlated inversely with ERK1/2 phosphorylation during progression. Taken together, our findings suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Mig-6 Suppresses Endometrial Cancer Associated with Pten Deficiency and ERK Activation

et al. 2014

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“…The nongenomic action of E2 has been linked to numerous pathways (EGFR, IGF-IR, c-MET) resulting in the activation of two key signaling cascades, the PTEN/PI3K/AKT and the MAPK pathways (Bhat-Nakshatri et al , 2008; Cheskis et al , 2008; Freeman et al , 2006; Thomas et al , 2008; Vilgelm et al , 2006). One consequence of this nongenomic E2 action is an inhibition of cellular apoptosis which has been observed in various cell types, such as vascular endothelial, smooth and skeletal muscles, and breast cancer cells (Bjornstrom and Sjoberg, 2005; Boland et al , 2008; Song and Santen, 2003; Spyridopoulos et al , 1997). MAPK/ERK-kinases (MEKs) trigger the activation of ERKs by phosphorylating a threonine and a tyrosine in their activation loop.…”

Section: Discussionmentioning

confidence: 99%

The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression

et al. 2010

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Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. An additional endometrial cancer mouse model is generated by ablation of Pten (either as heterozygotes or by conditional uterine ablation). To determine the interplay between Mig-6 and the PTEN/PI3K signaling pathway during endometrial tumorigenesis, we have generated mice with Mig-6 and Pten conditionally ablated in progesterone receptor positive cells (PRcre/+Mig-6f/fPtenf/f ; Mig-6d/dPtend/d). The ablation of both Mig-6 and Pten dramatically accelerated the development of endometrial cancer compared to single ablation of either gene. The epithelium of Mig-6d/dPtend/d mice showed a significant decrease in the number of apoptotic cells compared to Ptend/d mice. The expression of the estrogen-induced apoptotic inhibitors Birc1 was significantly increased in the Mig-6d/dPtend/d mice. We identified ERK2 as a MIG-6 interacting protein by co-immunoprecipitation and demonstrated that the level of ERK2 phosphorylation was increased upon Mig-6 ablation either singly or in combination with Pten ablation. These results suggest that Mig-6 exerts a tumor suppressor function in endometrial cancer by promoting epithelial cell apoptosis through the down-regulation of the estrogen-induced apoptosis inhibitors Birc1 and the inhibition of ERK2 phosphorylation.

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“…As a potent inhibitory signal for apoptosis in several kinds of cells, Akt might play an important role in regulating chondrocyte apoptosis or survival and potentially preventing OA [5]. Meanwhile, mounting evidence has indicated that E2 could regulate cell metabolism including cell proliferation through several signaling cascades in some cell lines [6,7]. Our hypothesis was that if the PI3K/Akt pathway plays an important role in the prevention of apoptosis or promotion of survival, then it is true: Akt contribution is behind the effect of E2.…”

Section: Introductionmentioning

confidence: 99%

17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway

Huang¹,

Xia

Zheng

et al. 2011

Cellular and Molecular Biology Letters

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Osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability. The importance of chondrocytes in the pathogenesis of OA is unequivocal. 17β-estradiol (E2) has a potential protective effect against OA. However, the mechanism of E2 in OA chondrocytes remains unclear. In this study, we investigated the regulative effect of E2 on cell growth and the relationship between E2 and the PI3K/Akt pathway in rat OA model chondrocytes (pretreated with interleukin-1β). We found that E2 induced chondrocyte proliferation, and increased the expression level of Akt simultaneously, especially the expression level of P-Akt. Furthermore, the inhibition of P-Akt could block chondrocyte proliferation induced by E2. These results suggest that PI3K/Akt activation induced by E2 may be an important factor in the mechanism of E2 in cell proliferation in rat OA model chondrocytes, and help further understanding the role of E2 in OA progression.

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17β-Estradiol signaling in skeletal muscle cells and its relationship to apoptosis

Cited by 54 publications

References 18 publications

Mig-6 Suppresses Endometrial Cancer Associated with Pten Deficiency and ERK Activation

Mig-6 Suppresses Endometrial Cancer Associated with Pten Deficiency and ERK Activation

The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression

17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway

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