Vischioni Barbara, van der Valk Paul, Span Simone W, Kruyt Frank A E, Rodriguez Jose A, Giaccone Giuseppe
Department of Medical Oncology, VU University Medical Center, HV1081 Amsterdam, The Netherlands.
Hum Pathol. 2006 Jan;37(1):78-86. doi: 10.1016/j.humpath.2005.09.022. Epub 2005 Nov 17.
The family of inhibitor of apoptosis (IAP) proteins can suppress apoptosis induced by a variety of triggers. Among the IAPs, cIAP1, cIAP2, and XIAP have been characterized as inhibitors of specific caspases, and their expression, together with that of survivin, has been shown in several studies to play a role as tumor marker and prognostic factor for the survival of patients with cancer. Although survivin is usually not expressed in normal adult tissues, cIAP1, cIAP2, and XIAP have been found broadly expressed at messenger RNA level within normal cells. Here, we report an immunohistochemical study in a comprehensive panel of normal human tissues, and we confirm at the protein level the wide expression of IAPs. These results are consistent with a physiological role of IAPs in normal cells. Moreover, we show that IAPs' expression levels and localization patterns differ depending on the cell lineage. The variable subcellular localization of the IAPs within different cell types suggests that compartmentalization may contribute to regulate their function. The physiological role of these proteins should be further investigated to help tailor IAP-targeted therapeutic strategies for patients with cancer and circumvent possible side effects.
凋亡抑制蛋白（IAP）家族能够抑制多种触发因素诱导的细胞凋亡。在IAP中，cIAP1、cIAP2和XIAP已被鉴定为特定半胱天冬酶的抑制剂，并且在多项研究中，它们与生存素的表达一起，被证明可作为癌症患者生存的肿瘤标志物和预后因素。虽然生存素通常不在正常成人组织中表达，但已发现cIAP1、cIAP2和XIAP在正常细胞的信使RNA水平广泛表达。在此，我们报告了一项针对全面的正常人体组织样本的免疫组织化学研究，并在蛋白质水平证实了IAP的广泛表达。这些结果与IAP在正常细胞中的生理作用一致。此外，我们表明IAP的表达水平和定位模式因细胞谱系而异。IAP在不同细胞类型中的亚细胞定位不同，这表明区域化可能有助于调节它们的功能。这些蛋白质的生理作用应进一步研究，以帮助为癌症患者量身定制针对IAP的治疗策略，并规避可能的副作用。
