GRM1 is An Androgen-Regulated Gene and its Expression Correlates with Prostate Cancer Progression in Pre-Clinical Models.
GRM1 is An Androgen-Regulated Gene and its Expression Correlates with Prostate Cancer Progression in Pre-Clinical Models.
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GRM1 是一种雄激素调节基因，其表达与临床前模型中前列腺癌的进展相关。
DOI：
10.1158/1078-0432.ccr-16-0137
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Koochekpour,Shah
中科院分区：
文献类型：
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作者：
Shourideh,Mojgan;Azabdaftari,Gissou;Attwood,Kristopher;DePriest,Adam;Wadosky,KristineM;Gillard,BryanM;Karasik,Ellen;Heemers,Hannelore;Kyprianou,Natasha;Gelman,IrwinH;Corey,Eva;Vessella,RobertL;Mohler,JamesL;Koochekpour,Shah
目的我们最近发现谷氨酸受体GRM 1在去势抵抗性前列腺癌（CR-PCa）组织和细胞中高水平表达。在此，我们在临床前PCa模型中确定了GRM 1与AR、PSA和肿瘤生长、缓解和复发之间的关系。GRM 1表达的改变对PCa细胞生长、迁移和侵袭的影响也进行了研究。实验设计我们使用定量基因表达和免疫组化来确定GRM 1表达与AR、PSA和肿瘤生长之间的时间相关性，在CWR 22（n = 59）和LuCaP 35（n = 12）PCa异种移植物的CR进展期间。在GRM 1过表达或沉默的PCa细胞系中研究了GRM 1表达水平改变对生长、迁移和侵袭的影响。在存在或不存在的抗雄激素bicalutamine.ResultsWe发现，GRM 1的转录和组织表达直接相关的生长和AR和PSA的表达在激素敏感（HS），去势，CR肿瘤异种移植物中的DHT对GRM 1表达的影响。GRM 1过表达或沉默与PCa细胞增殖、迁移和侵袭直接相关。DHT通过AR依赖的方式增加GRM 1在HS-和CR-PCa细胞株中的表达。ConclusionsThis is a first report of GRM 1 as a androgen and AR-target gene. GRM 1表达与肿瘤生长、消退和复发直接相关，并可能有助于临床前模型中PCa的CR进展。需要进一步的研究来确定GRM 1作为PCa的药物靶点或生物标志物的效用。
PurposeWe recently demonstrated that glutamate receptor GRM1 was expressed at high levels in castration-resistant prostate cancer (CR-PCa) tissues and cells. Herein, we determined the relationship between GRM1 and AR, PSA, and tumor growth, remission, and recurrence in preclinical PCa models. The effect of alterations in GRM1 expression was also investigated on PCa cell growth, migration and invasion.Experimental DesignWe used quantitative gene expression and immunohistochemistry to define the temporal association between GRM1 expression and AR, PSA, and tumor growth during CR progression in CWR22 (n = 59) and LuCaP 35 (n = 12) PCa xenografts. The effect of alterations in GRM1 expression levels on growth, migration, and invasion was investigated in GRM1-overexpressed or -silenced PCa cell lines. The effect of DHT on GRM1 expression was determined in the presence or absence of the antiandrogen bicalutamide.ResultsWe found that GRM1 transcript and tissue expression directly correlated with growth and AR and PSA expression in hormone-sensitive (HS), castrated, and CR tumor xenografts. GRM1 overexpression or silencing directly correlated with PCa cell proliferation, migration, and invasion. DHT increased GRM1 expression via an AR-dependent manner in HS- and CR-PCa cell lines.ConclusionsThis is a first report of GRM1 as an androgen and AR-target gene. GRM1 expression directly correlated with tumor growth, regression, and recurrence and may contribute to CR-progression of PCa in preclinical models. Further studies are needed to define the utility of GRM1 as a druggable target or biomarker for PCa.