Estrogen Receptor α (ERα) and Estrogen Related Receptor α (ERRα) are both transcriptional regulators of the Runx2-I isoform

Kammerer, Martial; Gutzwiller, Sabine; Stauffer, Daniela; Delhon, Isabelle; Seltenmeyer, Y; Fournier, Brigitte

doi:10.1016/j.mce.2013.01.024

Cited by 38 publications

(22 citation statements)

References 69 publications

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“…Indeed, evidence exists that the use of the two promoters is context dependent. In particular, our group and others have shown that RUNX2 isoform I is the major RUNX2 isoform in tumor cells, while isoform II seems to be restricted to skeletal cells (16,26). Noticeably, the majority of molecular signals known to control RUNX2 act through the P1 promoter, while the regulation of the P2 promoter remains largely unknown (28)(29)(30).…”

Section: Introductionmentioning

confidence: 92%

“…The two isoforms differ for only a few aminoacids at the N-terminal regions, even though differences in their activity were reported. The existence of two alternative promoters suggests that the expression of the two isoforms is regulated through different mechanisms (24)(25)(26)(27). Indeed, evidence exists that the use of the two promoters is context dependent.…”

Section: Introductionmentioning

confidence: 99%

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Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2

Sancisi¹,

Gandolfi²,

Ambrosetti

et al. 2015

Cancer Research

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Aberrant reactivation of embryonic pathways occurs commonly in cancer. The transcription factor RUNX2 plays a fundamental role during embryogenesis and is aberrantly reactivated during progression and metastasization of different types of human tumors. In this study, we attempted to dissect the molecular mechanisms governing RUNX2 expression and its aberrant reactivation. We identified a new regulatory enhancer element, located within the RUNX2 gene, which is responsible for the activation of the RUNX2 promoter and for the regulation of its expression in cancer cells. Furthermore, we have shown that treatment with the anticancer compounds histone deacetylase inhibitor (HDACi) results in a profound inhibition of RUNX2 expression, which is determined by the disruption of the transcription-activating complex on the identified enhancer. These data envisage a possible targeting strategy to counteract the oncongenic function of RUNX2 in cancer cells and provide evidence that the cytotoxic activity of HDACi in cancer is not only dependent on the reactivation of silenced oncosuppressors but also on the repression of oncogenic factors that are necessary for survival and progression.Cancer Res; 75(9); 1868-82. Ó2015 AACR.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2

Sancisi¹,

Gandolfi²,

Ambrosetti

et al. 2015

Cancer Research

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“…It is well known that ER levels and emplacement of breast tumor metastasis are the fundamental and critical determinants of clinical outcome, with high prognostic values having the greatest impact on patient survival chances (31,32). The importance of ERs as breast carcinoma biomarkers is also due to the ability of the hormone receptor protein to provide detailed information about breast tumor subtype.…”

Section: Er Proteins and Tumor Diseasesmentioning

confidence: 99%

Identification of estrogen receptor proteins in breast cancer cells using matrix-assisted laser desorption/ionization time of flight mass spectrometry (Review)

et al. 2014

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Estrogen receptors [ERs (subtypes α and β)], classified as a nuclear receptor super family, are intracellular proteins with an important biological role as the transcription factors for estrogen target genes. For ER-induced transcription, an interaction must exist between ligand and coregulators. Coregulators may stimulate (coactivators) or inhibit (corepressors) transcription, following binding with a specific region of the gene, called the estrogen response element. Misbalanced activity of coregulators or higher ligand concentrations may cause increased cell proliferation, resulting in specific types of cancer. These are exhibited as overexpression of ER proteins. Breast cancer currently ranks first in the incidence and second in the mortality of cancer in females worldwide. In addition, 70% of breast tumors are ERα positive and the importance of these proteins for diagnostic use is indisputable. Early diagnosis of the tumor and its classification has a large influence on the selection of appropriate therapy, as ER-positive tumors demonstrate a positive response to hormonal therapy. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI TOF MS) has been hypothesized to have great potential, as it offers reliable, robust and efficient analysis methods for biomarker monitoring and identification. The present review discusses ER protein analysis by MALDI TOF MS, including the crucial step of protein separation.

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“…The molecular mechanism through which ERRα exerts this activity is unclear, although it has been shown that the receptor can block the transcriptional activities of Runx2 [52]. In addition, ERRα inhibits Runx2 expression when combined to PGC-1β, whereas it exerts an opposite effect in the presence of PGC-1α, again pointing out to divergent outputs according to the coactivator involved [53]. Interestingly, ERRγ can also block ex vivo osteoblast differentiation by inhibiting Runx2 activity [54,55], although it is unknown whether these functions are also exerted in vivo.…”

Section: Errs and Adipocyte Differentiationmentioning

confidence: 99%

The estrogen-related receptors and the adipocyte

Carnesecchi

Vanacker

2013

Hormone Molecular Biology and Clinical Investigation

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The estrogen-related receptors (ERRα, β, and γ) are orphan members of the nuclear receptor superfamily. ERRα and γ are highly expressed in tissues displaying elevated energy demands and are involved in several aspects of energetic metabolism, which they regulate mostly in association with members of the PGC-1 coactivator family. These activities have mostly been documented in the liver, heart, or skeletal muscle. ERRα and γ are also highly expressed in adipocytes. Their precise roles in this cell type are less documented, although published data indicate that they contribute to cell differentiation as well as functionality. This review describes these activities.

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Estrogen Receptor α (ERα) and Estrogen Related Receptor α (ERRα) are both transcriptional regulators of the Runx2-I isoform

Cited by 38 publications

References 69 publications

Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2

Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2

Identification of estrogen receptor proteins in breast cancer cells using matrix-assisted laser desorption/ionization time of flight mass spectrometry (Review)

The estrogen-related receptors and the adipocyte

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