Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo

Sun, Junyan; Wang, Dongmei; Guo, Long; Fang, Shengyun; Wang, Yang; Rong, Xing

doi:10.3389/fnins.2017.00116

Cited by 8 publications

(10 citation statements)

References 30 publications

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“…Therefore, we have investigated the influence of both hormones on the expression of the SHANK genes, which are strongly linked to ASD pathology (Leblond et al, 2014 ). We could show in the SH-SY5Y neuroblastoma cell line, a widely used neuronal cell model to investigate hormonal influences of androgens and estrogens (Sarachana et al, 2011 ; Grassi et al, 2013 ; Nakaso et al, 2014 ; Sun et al, 2017 ), that the effect of DHT and 17β-estradiol on the expression of all three Shanks could be effectively blocked by androgen and estrogen receptor antagonists. SHANK gene expression was shown to be regulated by DHT, directly modulated by AR signaling.…”

Section: Discussionmentioning

confidence: 99%

Sex Hormones Regulate SHANK Expression

Berkel

Eltokhi

Fröhlich

et al. 2018

Front. Mol. Neurosci.

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Autism spectrum disorders (ASD) have a higher prevalence in male individuals compared to females, with a ratio of affected boys compared to girls of 4:1 for ASD and 11:1 for Asperger syndrome. Mutations in the SHANK genes (comprising SHANK1, SHANK2 and SHANK3) coding for postsynaptic scaffolding proteins have been tightly associated with ASD. As early brain development is strongly influenced by sex hormones, we investigated the effect of dihydrotestosterone (DHT) and 17β-estradiol on SHANK expression in a human neuroblastoma cell model. Both sex hormones had a significant impact on the expression of all three SHANK genes, which could be effectively blocked by androgen and estrogen receptor antagonists. In neuron-specific androgen receptor knock-out mice (ArNesCre), we found a nominal significant reduction of all Shank genes at postnatal day 7.5 in the cortex. In the developing cortex of wild-type (WT) CD1 mice, a sex-differential protein expression was identified for all Shanks at embryonic day 17.5 and postnatal day 7.5 with significantly higher protein levels in male compared to female mice. Together, we could show that SHANK expression is influenced by sex hormones leading to a sex-differential expression, thus providing novel insights into the sex bias in ASD.

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Section: Discussionmentioning

confidence: 99%

Sex Hormones Regulate SHANK Expression

Berkel

Eltokhi

Fröhlich

et al. 2018

Front. Mol. Neurosci.

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“…Our previous study suggested that NB cells may produce androgens for the growth of themselves ( 6 ). Here the production of hormones of cultured SH-SY5Y cells in comparison with HepG2 cells were determined with LC-MS/MS analysis.…”

Section: Resultsmentioning

confidence: 99%

“…In the previous study, we found that the androgen receptor (AR) agonist, R1881, promoted the growth of NB in vitro and in vivo and the AR antagonists, MDV3100 and ARN509, significantly decreased the proliferation, migration, invasion, and sphere formation of NB cells cultured in hormone-free medium ( 6 ). The findings suggested that NB cells were able to produce androgens for the growth of themselves.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effect of Statins and Abiraterone Acetate on the Growth Inhibition of Neuroblastoma via Targeting Androgen Receptor

Chen

Wang

et al. 2021

Front. Oncol.

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Neuroblastoma is the most common extracranial neuroendocrine tumor in childhood. Although many studies have tried to find effective treatments, there are still numerous limitations in current clinical targeted therapy. So, it is important to find new therapeutic targets and strategies from a new perspective. Our previous study reported that the androgen receptor (AR) promotes the growth of neuroblastoma in vitro and in vivo. Based on documentary investigation, we postulated that the AR–SCAP–SREBPs-CYP17/HMGCR axis may regulate cholesterol and androgens synthesis and form a positive enhancement loop promoting NB progression. Clinical samples and Oncomine database analysis proved the activation of AR–SCAP–SREBPs-CYP17/HMGCR axis in neuroblastoma. The combination of inhibitors of HMGCR (statins) and CYP17A1 (abiraterone acetate) showed synergistic effect that significantly inhibited the proliferation and migration with decreased expression of related genes detected in vitro and in vivo suggesting the dual-targeted therapy had the potential to inhibit the progression of neuroblastoma in spite of its MYCN status. This study provides new ideas for clinical treatment of neuroblastoma with efficacy and reduced toxicity.

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“…For example, being male sex hormones, androgens are responsible for the development of adult sexual functions and distinguishing of the male reproductive system. Moreover, androgens are required for various anabolic functions in several tissues/organs such as the muscle, bone (Chang et al, ; Takayama ) and the brain (Chang et al, ; Fargo, Galbiati, Foecking, Poletti, Jones Kathryn, , Gaignard et al, ). Multiple clinical cohorts reported that age‐related decline of serum androgen specifically promoted the development of Alzheimer's disease (AD; George, Petit, Gouras, Brundin, & Olsson, ; Rosario et al, ; César Vieira Juliany et al, ; Wahjoepramono et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…We have reported that PSF/SFPQ, an RNA‐binding protein, is implicated in AR signaling because of its ability to splice RNA and consequently regulate epigenetic conditions (Takayama et al, ). In the present study, we explored the regulatory mechanisms of APP expression associated with AR and PSF using SH‐SY5Y cells derived from the human neurons (Butler, Leigh, & Gallo, ; Matsumoto et al, ), which express endogenous AR and exhibit androgen‐dependent cell growth (Sun et al, ). Moreover, as in previous reports (Ke et al, ; Liang et al, ; Moosecker et al, ), the expression and function of several key factors such as APP and Tau proteins have been analyzed in SH‐SY5Y cells.…”

Section: Introductionmentioning

confidence: 99%

Amyloid precursor protein, an androgen‐regulated gene, is targeted by RNA‐binding protein PSF/SFPQ in neuronal cells

2019

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Amyloid precursor protein (APP) is a representative gene related to Alzheimer's disease (AD). Androgens function by binding to the androgen receptor (AR). Both androgen and RNA‐binding protein PSF play a role in the pathology of AD. However, the involvement of AR and PSF in APP regulation in neuron has not been investigated. Here, we explored the regulatory mechanism of APP expression by AR and PSF using neuron‐derived cells. We demonstrated that androgen up‐regulates the production of APP at the mRNA and protein levels. This induction is enhanced by AR over‐expression and inhibited by its silencing. One candidate AR‐binding region was identified in the intron region of APP and validated its activity as AR‐dependent enhancer by the luciferase assay. Furthermore, the public transcriptome data of brain tissues of mice indicated that APP is regulated by PSF post‐transcriptionally. We observed a decreased expression of APP after PSF knockdown and interaction of PSF with the APP transcript. Moreover, we revealed that silencing of PSF inhibited the stability of the APP mRNA. Thus, these results presented a new regulatory mechanism of APP expression by androgen through AR‐mediated transcription and PSF at the post‐transcriptional level that might be associated with the occurrence of AD.

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Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo

Cited by 8 publications

References 30 publications

Sex Hormones Regulate SHANK Expression

Sex Hormones Regulate SHANK Expression

Synergistic Effect of Statins and Abiraterone Acetate on the Growth Inhibition of Neuroblastoma via Targeting Androgen Receptor

Amyloid precursor protein, an androgen‐regulated gene, is targeted by RNA‐binding protein PSF/SFPQ in neuronal cells

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