Transforming events in thyroid tumorigenesis and their association with follicular lesions
Transforming events in thyroid tumorigenesis and their association with follicular lesions
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DOI：
10.1210/jc.86.10.5025
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发表时间：
2001-10-01
影响因子：
5.8
通讯作者：
Horwitz, G
中科院分区：
文献类型：
--
作者：
Heaney, AP;Nelson, V;Horwitz, G
甲状腺肿瘤包括广泛的肿瘤表型，其发病机制涉及不同的分子事件。垂体瘤转化基因最初分离自GH（4）垂体细胞，在体内具有致瘤性，调节碱性成纤维细胞生长因子的分泌，并与染色单体分离的securin抑制剂同源。垂体瘤转化基因1在几种正常人体组织中低水平表达，并且在肿瘤中大量表达，包括结肠直肠癌，其中垂体瘤转化基因表达与肿瘤侵袭性高度相关。由于垂体瘤转化基因受E调节，甲状腺癌显示出很强的女性优势，我们研究了垂体瘤转化基因1在人甲状腺肿瘤和正常人和大鼠甲状腺细胞中的表达和作用。垂体肿瘤转化基因1表达的增加在甲状腺肿瘤的早期就很明显，在甲状腺增生、滤泡性腺瘤和滤泡性癌中表达最丰富（1.8倍; P < 0.0001）。垂体瘤转化基因1在大鼠FRTL 5甲状腺细胞和原代人甲状腺细胞培养物中的过表达导致体外转化并产生去分化肿瘤表型。我们认为垂体瘤转化基因过表达可能在导致垂体瘤分化发展的早期分子事件中起作用。滤泡状和乳头状癌。
Thyroid tumors comprise a broad spectrum of neoplastic phenotypes, and distinct molecular events have been implicated in their pathogenesis. Pituitary tumor transforming gene, originally isolated from GH(4) pituitary cells, is tumorigenic in vivo, regulates basic fibroblast growth factor secretion, and is homologous to a securin inhibitor of chromatid separation. Pituitary tumor transforming gene 1 is expressed at low levels in several normal human tissues and is abundantly expressed in neoplasms, including colorectal carcinoma, where pituitary tumor transforming gene expression correlated highly with tumor invasiveness. As pituitary tumor transforming gene is regulated by E and as thyroid cancer shows a strong female preponderance, we examined pituitary tumor transforming gene 1 expression and action in human thyroid tumors and in normal human and rat thyroid cells. Increased pituitary tumor transforming gene 1 expression was evident early in thyroid tumors and was most abundantly expressed in a subset of thyroid hyperplasia, follicular adenomas, and follicular carcinomas (1.8-fold; P < 0.0001). Pituitary tumor transforming gene 1 overexpression in rat FRTL5 thyroid cells and in primary human thyroid cell cultures causes in vitro transformation and produces a dedifferentiated neoplastic phenotype.As pituitary tumor transforming gene 1 was abundantly overexpressed in follicular adenoma and follicular carcinoma, we propose that pituitary tumor transforming gene overexpression may play a role in the early molecular events leading to divergent development of follicular and papillary carcinoma.