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The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147940 | GEO | 2021/03/21

REPOSITORIES: GEO

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The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer [ChIP-seq]

Project description:To study androgen receptor transcriptomic activation in the presence of androgen in bladder cancer cell lines. A uniquely derived AR expressing clone of the bladder cancer cell line UMUC3 was derived and validated prior to ChIP-seq experiments. Androgen receptor chromatin immunoprecipitation (AR ChIP-seq) was used to determine the overall expression changes in repsonse to treatment with synthetic androgen. Evaluation of genes associated with androgen receptor stimulation were used for focused analysis when combined with microarray data.

2021-03-21 | GSE147939 | GEO

The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer [gene expression]

Project description:To study androgen receptor transcriptomic activation in the presence of androgen in bladder cancer cell lines. A uniquely derived AR expressing clone of the bladder cancer cell line UMUC3 was derived and validated prior to microarray experiments. Microarrays were used to determine the overall expression changes in repsonse to treatment with synthetic androgen. Evaluation of genes associated with androgen receptor stimulation were used for focused analysis when combined with ChIP-seq data.

2021-03-21 | GSE147938 | GEO

Androgen Receptor Regulates CD44 Expression in Bladder Cancer.

Project description:The androgen receptor (AR) is important in the development of both experimental and human bladder cancer. However, the role of AR in bladder cancer growth and progression is less clear, with literature indicating that more advanced stage and grade disease are associated with reduced AR expression. To determine the mechanisms underlying these relationships, we profiled AR-expressing human bladder cancer cells by AR chromatin immunoprecipitation sequencing and complementary transcriptomic approaches in response to in vitro stimulation by the synthetic androgen R1881. In vivo functional genomics consisting of pooled shRNA or pooled open reading frame libraries was employed to evaluate 97 genes that recapitulate the direction of expression associated with androgen stimulation. Interestingly, we identified CD44, the receptor for hyaluronic acid, a potent biomarker and driver of progressive disease in multiple tumor types, as significantly associated with androgen stimulation. CRISPR-based mutagenesis of androgen response elements associated with CD44 identified a novel silencer element leading to the direct transcriptional repression of CD44 expression. In human patients with bladder cancer, tumor AR and CD44 mRNA and protein expression were inversely correlated, suggesting a clinically relevant AR-CD44 axis. Collectively, our work describes a novel mechanism partly explaining the inverse relationship between AR and bladder cancer tumor progression and suggests that AR and CD44 expression may be useful for prognostication and therapeutic selection in primary bladder cancer. SIGNIFICANCE: This study describes novel AREs that suppress CD44 and an expected inverse correlation of AR-CD44 expression observed in human bladder tumors.

| S-EPMC8782536 | biostudies-literature

The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer

Project description:The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer

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The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer [ChIP-seq]

Project description:The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer [ChIP-seq]

| PRJNA622581 | ENA

The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer [gene expression]

Project description:The Androgen Receptor Directly Regulates CD44 Expression in Androgen Sensitive Bladder Cancer [gene expression]

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The metastasis suppressor NDRG1 directly regulates androgen receptor signaling in prostate cancer.

Project description:N-myc-downregulated gene 1 (NDRG1) has potent anticancer effects and inhibits cell growth, survival, metastasis, and angiogenesis. Previous studies suggested that NDRG1 is linked to the androgen signaling network, but this mechanistic relationship is unclear. Considering the crucial role of the androgen receptor (AR) in prostate cancer (PCa) progression, here we examined for the first time the effect of NDRG1 on AR expression, activation, and downstream signaling in LNCaP, 22Rv1, and C4-2B PCa cell types. We demonstrate that NDRG1 effectively promotes interaction of AR with the chaperone HSP90, which in turn stabilizes the AR while decreasing its androgen-mediated activation. The expression of NDRG1 suppressed: (1) AR activation, as measured by p-ARSer213 and p-ARSer81; (2) expression of a major AR transcriptional target, prostate-specific antigen (PSA); and (3) AR transcriptional activity, probably via inhibiting the c-Jun-AR interaction by reducing c-Jun phosphorylation (p-c-JunSer63). NDRG1 was also demonstrated to inhibit multiple key molecules involved in androgen-dependent and -independent signaling (namely EGFR, HER2, HER3, PI3K, STAT3, and NF-κB), which promote the development of castration-resistant prostate cancer. We also identified the cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domain of NDRG1 as vital for inhibition of AR activity. Examining NDRG1 and p-NDRG1 in PCa patient specimens revealed a significant negative correlation between NDRG1 and PSA levels in prostatectomy patients that went on to develop metastasis. These results highlight a vital role for NDRG1 in androgen signaling and its potential as a key therapeutic target and biomarker in PCa.

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-03 | GSE205150 | GEO

Androgen Receptor Signaling in Bladder Cancer.

Project description:Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer.

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The androgen receptor regulates a druggable translational regulon in advanced prostate cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-07-31 | GSE116083 | GEO