BACKGROUND Revealing molecular mechanisms linked to androgen receptor activity can help to improve diagnosis and treatment of prostate cancer. Retinoic acid-induced 2 (RAI2) protein is thought to act as a transcriptional coregulator involved in hormonal responses and epithelial differentiation. We evaluated the clinical relevance and biological function of the RAI2 protein in prostate cancer. METHODS We assessed RAI2 gene expression in the Cancer Genome Atlas prostate adenocarcinoma PanCancer cohort and protein expression in primary tumors (n = 199) by immunohistochemistry. We studied RAI2 gene expression as part of a multimarker panel in an enriched circulating tumor cell population isolated from blood samples (n = 38) of patients with metastatic prostate cancer. In prostate cancer cell lines, we analyzed the consequences of androgen receptor inhibition on RAI2 protein expression and the consequences of RAI2 depletion on the expression of the androgen receptor and selected target genes. RESULTS Abundance of the RAI2 protein in adenocarcinomas correlated with the androgen receptor; keratins 8, 18, and 19; and E-cadherin as well as with an early biochemical recurrence. In circulating tumor cells, detection of RAI2 mRNA significantly correlated with gene expression of FOLH1, KLK3, RAI2, AR, and AR-V7. In VCaP and LNCaP cell lines, sustained inhibition of hormone receptor activity induced the RAI2 protein, whereas RAI2 depletion augmented the expression of MME, STEAP4, and WIPI1. CONCLUSIONS The RAI2 protein functions as a transcriptional coregulator of the androgen response in prostate cancer cells. Detection of RAI2 gene expression in blood samples from patients with metastatic prostate cancer indicated the presence of circulating tumor cells.

中文翻译：

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维甲酸诱导的2在前列腺癌中的表达模式和辅阻遏功能。

背景揭示与雄激素受体活性相关的分子机制可以帮助改进前列腺癌的诊断和治疗。视黄酸诱导的 2 (RAI2) 蛋白被认为是参与激素反应和上皮分化的转录辅助调节剂。我们评估了RAI2蛋白在前列腺癌中的临床相关性和生物学功能。方法 我们通过免疫组织化学评估癌症基因组图谱前列腺腺癌 PanCancer 队列中的 RAI2 基因表达和原发性肿瘤 (n = 199) 中的蛋白质表达。我们研究了 RAI2 基因表达，作为多标志物组的一部分，从转移性前列腺癌患者的血液样本 (n = 38) 中分离出的富集循环肿瘤细胞群。在前列腺癌细胞系中，我们分析了雄激素受体抑制对 RAI2 蛋白表达的影响以及 RAI2 耗竭对雄激素受体和选定靶基因表达的影响。结果腺癌中RAI2蛋白的丰度与雄激素受体相关；角蛋白 8、18 和 19；和 E-cadherin 以及早期生化复发。在循环肿瘤细胞中，RAI2 mRNA 的检测与 FOLH1、KLK3、RAI2、AR 和 AR-V7 的基因表达显着相关。在 VCaP 和 LNCaP 细胞系中，激素受体活性的持续抑制诱导了 RAI2 蛋白，而 RAI2 消耗增加了 MME、STEAP4 和 WIPI1 的表达。结论 RAI2 蛋白在前列腺癌细胞中作为雄激素反应的转录共调节因子发挥作用。