Expression and function of Cbfa-1/Runx2 in thyroid papillary carcinoma cells
Expression and function of Cbfa-1/Runx2 in thyroid papillary carcinoma cells
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DOI：
10.1210/jc.2007-2805
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发表时间：
2008-06-01
影响因子：
5.8
通讯作者：
Kobayashi, Tetsuro
中科院分区：
文献类型：
--
作者：
Endo, Toyoshi;Ohta, Kazuyasu;Kobayashi, Tetsuro
背景：钙化灶的形成是人类甲状腺乳头状癌的常见现象，但其机制仍不清楚。目的：因此，我们研究了骨钙素和/或 Cbfa-1 基因是否在恶性甲状腺上皮细胞中表达。我们还研究了Cbfa-1对甲状腺细胞中成骨细胞特异性和促甲状腺素受体基因表达的影响。结果：人甲状腺乳头状癌细胞系BHP18-21表达骨型骨钙素mRNA的水平高于MG63骨肉瘤细胞。使用 BHP18-21 细胞和 FRTL-5 细胞的核提取物进行的 Northern 印迹分析和 EMSA 表明，甲状腺上皮来源的细胞表达 Cbfa-1/Runx2，这是表达骨钙素的主要转录因子。当我们将pcDNA3.1-人Cbfa-1转染至FRTL-5细胞时，Cbfa-1增加了碱性磷酸酶、I型胶原和骨钙素的基因表达，但抑制了促甲状腺素受体的表达。然后，我们用抗骨钙素抗体对人乳头状甲状腺癌组织的钙化区域进行染色，发现恶性细胞以及滤泡上皮细胞对骨钙素呈免疫阳性。 Northern印迹分析显示，Cbfa-1/Runx2基因在4例手术切除的乳头状癌组织中强表达。结论：甲状腺细胞与成骨细胞具有相同的特征。 Cbfa-1 可能在人甲状腺乳头状癌组织的钙化过程中发挥作用。
Context: Development of calcifying foci is a common finding in human thyroid papillary carcinoma, but its mechanisms remain unknown.Objective: We therefore investigated whether osteocalcin and/or Cbfa-1 genes are expressed in malignant thyroid epithelial cells. We also studied the effects of Cbfa-1 on the expression of osteoblast-specific and thyrotropin receptor genes in thyrocytes.Results: The human thyroid papillary carcinoma cell line BHP18-21 expresses bone-type osteocalcin mRNA at higher levels than in MG63 osteosarcoma cells. Northern blot analysis and EMSA using nuclear extracts from BHP18-21 cells and FRTL-5 cells demonstrated that cells of thyroid epithelial origin expressed Cbfa-1/Runx2, the main transcription factor for the expression of osteocalcin. When we transfected pcDNA3.1-human Cbfa-1 into FRTL-5 cells, Cbfa-1 increased the gene expression of alkaline phosphatase, type I collagen, and osteocalcin but suppressed the expression of thyrotropin receptor. We then stained the calcified regions of human papillary thyroid carcinoma tissues with antiosteocalcin antibody and found that malignant cells, as well as follicular epithelial cells, were immunopositive for osteocalcin. Northern blot analysis revealed that the Cbfa-1/Runx2 gene was strongly expressed in tissues from four cases of surgically resected papillary carcinoma.Conclusions: Thyrocytes share characteristics with osteoblasts. Cbfa-1 may play a role in calcification processes in human thyroid papillary carcinoma tissues.