Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Clin Chem. 2022 Jul 3;68(7):973-983. doi: 10.1093/clinchem/hvac073.
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.
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.
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.
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.
揭示与雄激素受体活性相关的分子机制有助于改善前列腺癌的诊断和治疗。维甲酸诱导基因 2（RAI2）蛋白被认为是一种转录共激活因子，参与激素反应和上皮分化。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。
我们评估了癌症基因组图谱前列腺腺癌 PanCancer 队列中的 RAI2 基因表达，并通过免疫组织化学检测了原发性肿瘤（n=199）中的 RAI2 蛋白表达。我们研究了 RAI2 基因表达作为从转移性前列腺癌患者血液样本中分离的富集循环肿瘤细胞群中多标记面板的一部分（n=38）。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。
腺癌中 RAI2 蛋白的丰度与雄激素受体、角蛋白 8、18 和 19 以及 E-钙黏蛋白以及早期生化复发相关。在循环肿瘤细胞中，RAI2 mRNA 的检测与 FOLH1、KLK3、RAI2、AR 和 AR-V7 的基因表达显著相关。在 VCaP 和 LNCaP 细胞系中，持续抑制激素受体活性诱导 RAI2 蛋白，而 RAI2 耗竭则增强了 MME、STEAP4 和 WIPI1 的表达。
RAI2 蛋白在前列腺癌细胞的雄激素反应中作为转录共激活因子发挥作用。在转移性前列腺癌患者的血液样本中检测到 RAI2 基因表达表明存在循环肿瘤细胞。
