Androgen signalling and steroid receptor crosstalk in endocrine cancers

Claessens, Frank; Tilley, Wayne D.

doi:10.1530/erc-14-0274

Cited by 6 publications

(6 citation statements)

References 17 publications

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“…While inhibition of MCL proliferation by enzalutamide may occur via direct AR inhibition, it may also occur indirectly via inhibition of AR cross-talk with other steroid receptors such as ER, as observed in breast cancer models [24, 25]. …”

Section: Resultsmentioning

confidence: 99%

Androgen receptor expression in mantle cell lymphoma: Potential novel therapeutic implications

Mostaghel

Martin

Mongovin

et al. 2017

Experimental Hematology

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Section: Resultsmentioning

confidence: 99%

Androgen receptor expression in mantle cell lymphoma: Potential novel therapeutic implications

Mostaghel

Martin

Mongovin

et al. 2017

Experimental Hematology

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“…Emerging interests have started to focus on the crosstalk between AR and ER signaling in PC (Yang et al . 2012, Claessens and Tilley 2014, Nelson et al . 2014).…”

Section: Discussionmentioning

confidence: 99%

“…The actions of parenteral estrogens are believed to be mediated by the classical estrogen receptors (ERs), ESR1 and ESR2. However, the exact roles of the two ERs and its isoforms on PC growth and metastases may vary according to cellular contexts (Claessens and Tilley 2014, Nelson et al 2014). We recently reported that G-1 (1(1-[4-(6-bromobenzo[1,3]dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone), which selectively activates the third ER, G protein–coupled receptor 30 (GPR30 or GPER) (Bologa et al 2006), inhibited the growth of multiple PC cell lines and PC-3 xenografts, and exerted few or no adverse effects on the animals (Chan et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Targeting GPR30 with G-1: a new therapeutic target for castration-resistant prostate cancer

Lam¹,

Ouyang²,

Chen³

et al. 2014

Endocrine-Related Cancer

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Castration-resistant prostate cancer (CRPC) is an advanced-stage prostate cancer (PC) associated with high mortality. We reported that G-1, a selective agonist of G protein-coupled receptor 30 (GPR30), inhibited PC cell growth by inducing G2 cell cycle arrest and arrested PC-3 xenograft growth. However, therapeutic actions of G-1 and their relationships with androgen in vivo are unclear. Using the LNCaP xenograft to model PC growth during androgen-sensitive (AS) versus castration-resistant (CR) phase, we found that G-1 inhibited growth of CR but not AS tumors with no observable toxicity to the host. Substantial necrosis (~65%) accompanied by marked intratumoral infiltration of neutrophils was observed only in CR tumors. Global transcriptome profiling of human genes identified 99 differential expressed genes with “interplay between innate and adaptive immune response” as the top pathway. Quantitative-PCR confirmed upregulation of neutrophil-related chemokines and inflammation-mediated cytokines only in the G-1-treated CR tumors. Expression of murine neutrophil-related cytokines also was elevated in these tumors. GPR30 expression was significantly higher in CR than AS tumors. In cell-based experiments, androgen repressed GPR30 expression, a response reversible by anti-androgen or siRNA-induced androgen receptor silencing. Finally, in clinical specimens, 80% of CRPC metastases (n=123) express a high level of GPR30 whereas only 54% of the primary PCs (n=232) showed high GPR30 expression. Together, these results provide the first evidence that GPR30 is an androgen-repressed target and G-1 mediates the anti-tumor effect via neutrophil infiltration-associated necrosis in CRPC. Additional studies are warranted to firmly establish GPR30 as a therapeutic target in CRPC.

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“…Estrogen has an efficacy for advanced prostate cancer (PC) via the mediation of the classical estrogen receptors [ 58 ]. The effects of ER on PC growth and metastases have different mechanisms in different cellular microenvironments [ 59 ]. The expression of GPER-1 is higher in the preneoplastic lesions and normal areas of benign prostate than the basal epithelial cells [ 60 ].…”

Section: Functions Of Gper-1 In Reproductive System Tumorsmentioning

confidence: 99%

Function of G-Protein-Coupled Estrogen Receptor-1 in Reproductive System Tumors

Qian

Xuan

Yuan

et al. 2016

Journal of Immunology Research

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The G-protein-coupled estrogen receptor-1 (GPER-1), also known as GPR30, is a novel estrogen receptor mediating estrogen receptor signaling in multiple cell types. The progress of estrogen-related cancer is promoted by GPER-1 activation through mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), and phospholipase C (PLC) signaling pathways. However, this promoting effect of GPER-1 is nonclassic estrogen receptor (ER) dependent manner. In addition, clinical evidences revealed that GPER-1 is associated with estrogen resistance in estrogen-related cancer patients. These give a hint that GPER-1 may be a novel therapeutic target for the estrogen-related cancers. However, preclinical studies also found that GPER-1 activation of its special agonist G-1 inhibits cancer cell proliferation. This review aims to summarize the characteristics and complex functions of GPER-1 in cancers.

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Androgen signalling and steroid receptor crosstalk in endocrine cancers

Cited by 6 publications

References 17 publications

Androgen receptor expression in mantle cell lymphoma: Potential novel therapeutic implications

Androgen receptor expression in mantle cell lymphoma: Potential novel therapeutic implications

Targeting GPR30 with G-1: a new therapeutic target for castration-resistant prostate cancer

Function of G-Protein-Coupled Estrogen Receptor-1 in Reproductive System Tumors

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