Dissecting the function of RAI2 in anti-androgen resistance in prostate cancer

剖析 RAI2 在前列腺癌抗雄激素抵抗中的功能

• 批准号: 439618222
• 负责人: Professor Dr. Klaus Pantel
• 金额: --
• 依托单位: Institut für Tumorbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/439618222?language=en
• 关键词: Dissecting; function; RAI2; anti; androgen

The RAI2 gene, which was initially identified at ITB in Hamburg as a novel tumor suppressor, holds potential as novel drug-able target and actionable marker of anti-androgen therapy. Molecular characterization of the RAI2 protein in luminal breast cell lines already revealed that it is acting as a transcriptional co-regulator involved in hormonal responses as well as in the response to genotoxic stress in breast cancer cells. Also other researcher have previously reported that integration of viral mouse mammary tumor virus (MMTV) into the RAI2 gene locus is associated with the emergence of recurrent and hormone-independent breast tumors, emphasizing a particular role for RAI2 depletion in the progression from hormone-dependent to hormone-independent tumors. Although RAI2 protein function in prostate cancer cells remains completely uncharacterized by now, first results show that it is likely to resemble a specific function also in hormone dependent prostate tumors. We hypothesize that loss of RAI2 function in androgen-dependent prostate tumors contributes to progress to hormone independence and metastasis formation. The key objective of this research project is therefore to analyse RAI2 protein function in hormone dependent prostate cancer cells and to dissect its potential role in anti-androgen resistance. In addition, we intend to determine RAI2 expression in prostate cancer samples and to evaluate the potential of RAI2 expression to serve as novel biomarker for prostate cancer therapies and to validate on large PCa patient cohorts the practicality of RAI2, AR-V7 and PSMA detection as blood-based biomarkers.

RAI 2基因最初在汉堡ITB被鉴定为一种新型肿瘤抑制因子，具有作为抗雄激素治疗的新型药物靶点和可操作标记物的潜力。在管腔乳腺细胞系中RAI 2蛋白的分子表征已经揭示，它作为转录辅助调节因子参与激素反应以及对乳腺癌细胞中遗传毒性应激的反应。其他研究人员先前也报道了病毒性小鼠乳腺肿瘤病毒（MMTV）整合到RAI 2基因座中与复发性和非乳腺癌依赖性乳腺肿瘤的出现相关，强调了RAI 2缺失在从乳腺癌依赖性肿瘤进展到非乳腺癌依赖性肿瘤中的特殊作用。虽然RAI 2蛋白在前列腺癌细胞中的功能目前还完全没有被表征，但初步结果表明，它可能类似于激素依赖性前列腺肿瘤中的特定功能。我们假设RAI 2功能的丧失在雄激素依赖性前列腺肿瘤中有助于激素非依赖性和转移形成的进展。因此，本研究项目的主要目标是分析RAI 2蛋白在激素依赖性前列腺癌细胞中的功能，并分析其在抗雄激素抵抗中的潜在作用。此外，我们打算确定前列腺癌样品中的RAI 2表达，并评估RAI 2表达作为前列腺癌治疗的新生物标志物的潜力，并在大型PCa患者队列中验证RAI 2、AR-V7和PSMA检测作为血液生物标志物的实用性。