Gene Expression Profiling Reveals Regulation of ERK Phosphorylation by Androgen-Induced Tumor Suppressor U19/EAF2 in the Mouse Prostate

Su, Fei; Corrêa, Bruna; Luo, Jianhua; Vêncio, Ricardo Zorzetto Nicoliello; Pascal, Laura E.; Wang, Zhou

doi:10.1007/s12307-013-0132-4

Cited by 15 publications

(11 citation statements)

References 53 publications

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“…Eaf2 loss was previously shown to activate the ERK pathway (Su, et al 2013). RTN4 is a neurite outgrowth inhibitor (Spillmann, et al 1998) that was shown to inhibit proliferation and promote apoptosis when transfected into human hepatocellular carcinoma cells (Chen, et al 2005).…”

Section: Discussionmentioning

confidence: 96%

Conditional deletion of ELL2 induces murine prostate intraepithelial neoplasia

Pascal

Masoodi

Liu

et al. 2017

Journal of Endocrinology

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Elongation factor, RNA polymerase II, 2 (ELL2) is an RNA Pol II elongation factor with functional properties similar to ELL that can interact with the prostate tumor suppressor EAF2. In the prostate, ELL2 is an androgen response gene that is up-regulated in benign prostatic hyperplasia (BPH). We recently showed that ELL2 loss could enhance prostate cancer cell proliferation and migration, and that ELL2 gene expression was down-regulated in high Gleason score prostate cancer specimens. Here, prostate-specific deletion of ELL2 in a mouse model revealed a potential role for ELL2 as a prostate tumor suppressor in vivo. Ell2 knockout mice exhibited prostatic defects including increased epithelial proliferation, vascularity and PIN lesions similar to the previously determined prostate phenotype in Eaf2 knockout mice. Microarray analysis of prostates from Ell2 knockout and wild-type mice on a C57BL/6J background at age 3 mos and qPCR validation at 17 mos of age revealed a number of differentially expressed genes associated with proliferation, cellular motility and epithelial and neural differentiation. OncoPrint analysis identified combined down-regulation or deletion in prostate adenocarcinoma cases from the Cancer Genome Atlas (TCGA) data portal. These results suggest that ELL2 and its pathway genes likely play an important role in the development and progression of prostate cancer.

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Section: Discussionmentioning

confidence: 96%

Conditional deletion of ELL2 induces murine prostate intraepithelial neoplasia

Pascal

Masoodi

Liu

et al. 2017

Journal of Endocrinology

Self Cite

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“…Inactivation of EAF2 induces tumorigenesis in several organs, including lung, liver and prostate [22]. Although its mechanism of action is unknown, studies show that EAF2 functions in controlling the growth and survival of cancer cells by negatively regulating canonical Wnt/β-catenin signaling as well as the RAS-BRAF-ERK signaling pathway [23, 24]. EAF2 also reportedly binds to and stabilizes von Hippel-Lindau protein (pVHL), a tumor suppressor involved in mediating HIF1α degradation and an inhibitor of the hypoxia pathway, which suggests it is a potential metabolic regulator [25].…”

Section: Introductionmentioning

confidence: 99%

EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling

et al. 2016

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Cancer cells prefer glycolysis for energy metabolism, even when there is sufficient oxygen to make it unnecessary. This is called the Warburg effect, and it promotes tumorigenesis and malignant progression. In this study, we demonstrated that EZH2, a multifaceted oncogenic protein involved in tumor proliferation, invasion and metastasis, promotes glioblastoma tumorigenesis and malignant progression through activation of the Warburg effect. We observed that HIF1α is a target of EZH2 whose activation is necessary for EZH2-mediated metabolic adaption, and that HIF1α is activated upon EZH2 overexpression. EZH2 suppressed expression of EAF2, which in turn upregulated HIF1α levels. We conclude from these results that EZH2 promotes tumorigenesis and malignant progression in part by activating glycolysis through an EAF2-HIF1α signaling axis.

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“…Of these genes, 49 had a statistically significant tendency to co‐occur in tumor specimens with ELL2 alteration, while two were mutually exclusive (Table ). None of the identified AR response genes were identified previously as also being regulated by ELL2 or EAF2 . Interestingly, only SPDEF and TM4SF1 were identified as having a statistically significant tendency to co‐occur with EAF2 alteration in prostate cancer specimens (data not shown).…”

Section: Resultsmentioning

confidence: 86%