Subramanian Mahesh, Pilli Tania, Bhattacharya Palash, Pacini Furio, Nikiforov Yuri E, Kanteti Prasad V, Prabhakar Bellur S
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
J Clin Endocrinol Metab. 2009 Apr;94(4):1467-71. doi: 10.1210/jc.2008-2378. Epub 2009 Feb 3.
The aim of the study was to investigate the expression and function of the IG20 gene in thyroid cancer cell survival, proliferation, and apoptosis.
We determined the expression levels of the major isoforms of IG20 by quantitative RT-PCR in normal and thyroid tumor tissues/cell lines. We evaluated the functional consequence of IG20 knockdown in WRO (follicular carcinoma) and FRO (anaplastic carcinoma) thyroid cancer cell lines by measuring spontaneous, TNFalpha-related apoptosis-inducing ligand (TRAIL), and TNFalpha-induced apoptosis.
The IG20 gene expression levels were higher in benign and malignant thyroid tumors and in WRO and FRO cells relative to normal tissues. Predominantly, MADD and DENN-SV isoforms of IG20 gene were expressed. IG20 knockdown resulted in increased spontaneous, TRAIL-, and TNFalpha-induced apoptosis in WRO, but not FRO, cells. FRO cell resistance to apoptosis is likely due to caspase-8 deficiency.
IG20 knockdown renders WRO cells more susceptible to spontaneous, TRAIL-, and TNFalpha-induced apoptosis and thus demonstrates the prosurvival function of the IG20 gene in thyroid cancer. These observations, combined with overexpression of IG20 noted in thyroid tumor tissues, may suggest a potential role in thyroid cancer survival and growth and indicate that IG20 may be targeted either alone or in conjunction with TRAIL or TNFalpha treatment in certain thyroid cancers.
本研究旨在探讨IG20基因在甲状腺癌细胞存活、增殖和凋亡中的表达及功能。
我们通过定量逆转录聚合酶链反应（RT-PCR）测定正常及甲状腺肿瘤组织/细胞系中IG20主要异构体的表达水平。我们通过检测自发凋亡、肿瘤坏死因子α相关凋亡诱导配体（TRAIL）及肿瘤坏死因子α诱导的凋亡，评估IG20基因敲低对WRO（滤泡癌）和FRO（未分化癌）甲状腺癌细胞系功能的影响。
与正常组织相比，IG20基因在良性和恶性甲状腺肿瘤以及WRO和FRO细胞中的表达水平更高。主要表达的是IG20基因的MADD和DENN-SV异构体。IG20基因敲低导致WRO细胞（而非FRO细胞）的自发凋亡、TRAIL诱导的凋亡及肿瘤坏死因子α诱导的凋亡增加。FRO细胞对凋亡的抗性可能归因于半胱天冬酶-8缺乏。
IG20基因敲低使WRO细胞对自发凋亡、TRAIL诱导的凋亡及肿瘤坏死因子α诱导的凋亡更敏感，从而证明IG20基因在甲状腺癌中的促存活功能。这些观察结果，结合甲状腺肿瘤组织中IG20的过表达，可能提示其在甲状腺癌存活和生长中的潜在作用，并表明在某些甲状腺癌中，IG20可能单独或与TRAIL或肿瘤坏死因子α联合治疗作为靶点。
