FOXA1 Is a Potential Oncogene in Anaplastic Thyroid Carcinoma
FOXA1 Is a Potential Oncogene in Anaplastic Thyroid Carcinoma
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DOI：
10.1158/1078-0432.ccr-08-3155
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发表时间：
2009-06-01
影响因子：
11.5
通讯作者：
Brown, Myles
中科院分区：
文献类型：
--
作者：
Nucera, Carmelo;Eeckhoute, Jerome;Brown, Myles
目的：FOXA1是一种哺乳动物内皮细胞转录因子，属于人类叉头盒基因家族，在某些肿瘤类型中发挥作用。在这里，我们研究了FOXA1在人类甲状腺癌中的潜在作用。实验设计：我们分别用免疫组织化学和荧光原位杂交法检测了FOXA1在甲状腺良性肿瘤和恶性甲状腺肿瘤中的表达水平和基因拷贝数。此外，我们通过短发夹状RNA介导的沉默来检测FOXA1在未分化的甲状腺癌细胞系增殖中的作用。结果：我们发现FOXA1在人类间变性甲状腺癌(ATC)中过表达。此外，我们在ATC细胞系和人类ATC病例中都发现了14q21.1基因座上FOXA1 DNA拷贝数的增加。在ATC细胞系中沉默FOXA1导致G(1)生长停滞和细胞增殖减少。结论：FOXA1在侵袭性甲状腺癌中过表达，参与了ATC细胞的细胞周期进程。因此，FOXA1可能是甲状腺肿瘤发生过程中的一个重要癌基因，也可能成为治疗甲状腺间变性癌的新靶点。
Purpose: FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene family that plays a role in certain tumor types. Here, we investigated the potential role of FOXA1 in human thyroid carcinomas.Experimental Design: We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in situ hybridization, respectively, in a cohort of benign and malignant thyroid tumors. In addition, we examined the role of FOXA1 in the proliferation of an undifferentiated thyroid carcinoma cell line by short hairpin RNA-mediated silencing.Results: We show that FOXA1 is overexpressed in human anaplastic thyroid carcinomas (ATC). In addition, we identify FOXA1 DNA copy number gain within the 14q21.1 locus in both an ATC cell line and human ATC cases. Silencing of FOXA1 in an ATC cell line causes G(1) growth arrest and reduction of cell proliferation. Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27(kip1) up-regulation on FOXA1 silencing.Conclusions: FOXA1 is overexpressed in aggressive thyroid cancers and involved in cell cycle progression in an ATC cell line. Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers.