Saadi Houda, Seillier Marion, Sandi Maria José, Peuget Sylvain, Kellenberger Christine, Gravis Gwenaëlle, Dusetti Nelson J, Iovanna Juan L, Rocchi Palma, Amri Mohamed, Carrier Alice
Inserm, U1068, CRCM, Marseille F-13009, France ; Institut Paoli-Calmettes, Marseille F-13009, France ; Aix-Marseille Université, Marseille F-13284, France ; CNRS, UMR7258, CRCM, Marseille F-13009, France ; Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Unité de Recherche 00/UR/08-01, Tunis, Tunisia ; Département des Sciences Biologiques, Faculté des Sciences de Tunis, Campus Universitaire, El Manar, Tunis 2092, Tunisia.
Inserm, U1068, CRCM, Marseille F-13009, France ; Institut Paoli-Calmettes, Marseille F-13009, France ; Aix-Marseille Université, Marseille F-13284, France ; CNRS, UMR7258, CRCM, Marseille F-13009, France.
Results Immunol. 2013 May 28;3:51-6. doi: 10.1016/j.rinim.2013.05.002. eCollection 2013.
Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) plays an important role during cell stress response in synergy with the potent "genome-keeper" p53. In human, the gene encoding TP53INP1 is expressed at very high level in some pathological situations, such as inflammation and prostate cancer (PC). TP53INP1 overexpression in PC seems to be a worse prognostic factor, particularly predictive of biological cancer relapse, making TP53INP1 a relevant specific target for molecular therapy of Castration Resistant (CR) PC. In that context, detection of TP53INP1 in patient biological fluids is a promising diagnostic avenue. We report here successful development of a new Enzyme-Linked Immunosorbent Assay (ELISA) detecting TP53INP1, taking advantage of molecular tools (monoclonal antibodies (mAbs) and recombinant proteins) generated in the laboratory during the course of basic functional investigations devoted to TP53INP1. The ELISA principle is based on a sandwich immunoenzymatic system, TP53INP1 protein being trapped by a first specific mAb coated on microplate then recognized by a second specific mAb. This new assay allows specific detection of TP53INP1 in serum of several PC patients. This breakthrough paves the way towards investigation of a large cohort of patients and assessment of clinical applications of TP53INP1 dosage.
肿瘤蛋白53诱导核蛋白1(TP53INP1)在细胞应激反应中与强大的“基因组守护者”p53协同发挥重要作用。在人类中,编码TP53INP1的基因在某些病理情况下,如炎症和前列腺癌(PC)中表达水平非常高。PC中TP53INP1的过表达似乎是一个更差的预后因素,尤其是预测癌症生物学复发,这使得TP53INP1成为去势抵抗性(CR)PC分子治疗的一个相关特异性靶点。在这种情况下,在患者生物体液中检测TP53INP1是一条有前景的诊断途径。我们在此报告成功开发了一种检测TP53INP1的新型酶联免疫吸附测定(ELISA),利用了在致力于TP53INP1的基础功能研究过程中实验室产生的分子工具(单克隆抗体(mAb)和重组蛋白)。ELISA原理基于夹心免疫酶系统,TP53INP1蛋白首先被包被在微孔板上的第一种特异性mAb捕获,然后被第二种特异性mAb识别。这种新方法能够特异性检测数例PC患者血清中的TP53INP1。这一突破为研究大量患者群体以及评估TP53INP1剂量的临床应用铺平了道路。