Pituitary tumor transforming gene binding factor: A novel transforming gene in thyroid tumorigenesis
Pituitary tumor transforming gene binding factor: A novel transforming gene in thyroid tumorigenesis
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DOI：
10.1210/jc.2005-0523
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发表时间：
2005-07-01
影响因子：
5.8
通讯作者：
McCabe, CJ
中科院分区：
文献类型：
--
作者：
Stratford, AL;Boelaert, K;McCabe, CJ
背景：目前还没有明确的标记物用于检测分化型甲状腺癌及其复发。甲状腺肿瘤转化基因（PTTG）是一种与多种肿瘤发病机制有关的原癌基因，它通过PTTG结合因子（PBF）刺激成纤维细胞生长因子-2（fibroblast growth factor-2，FGF-2）的分泌。在手术过程中收集组织，正常样本取自对侧叶。体外研究确定了PBF转化细胞和在裸鼠中形成肿瘤的能力及其亚细胞定位。设置：该研究在初级保健/转诊中心进行。患者：甲状腺肿瘤收集自一系列27例接受乳头状和滤泡状甲状腺肿瘤手术切除的患者。干预：未进行干预。主要结果测量：结果：PBF mRNA在分化型甲状腺癌中的表达高于正常甲状腺组织，而在分化型甲状腺癌中的表达高于正常甲状腺组织（P < 0.001; n = 27），与肿瘤复发独立相关（P = 0.002; R-2 = 0.49）。PTTG能显著上调PBF mRNA的表达（P < 0.001; n = 12），稳定过表达PBF的NIH 3 T3细胞集落形成率显著增高（P < 0.001; n = 12）。在体内，稳定的SC过表达PBF诱导肿瘤形成在athymic nude mice.Conclusions：PBF是一个额外的预后指标，分化型甲状腺癌是在体外转化和体内致瘤。
Context: There are currently no clear markers for the detection of differentiated thyroid cancer and its recurrence. Pituitary tumor transforming gene (PTTG) is a protooncogene implicated in the pathogenesis of multiple tumor types, which stimulates fibroblast growth factor-2 secretion via PTTG binding factor (PBF).Objective: The aim of this study was to ascertain whether PBF expression is associated with thyroid cancer outcome.Design: PBF expression was measured at the mRNA and protein level. Tissue was collected during surgery, with normal samples being taken from the contralateral lobe. In vitro studies ascertained the ability of PBF to transform cells and form tumors in nude mice and its subcellular localization.Setting: The study was conducted at a primary care/referral center.Patients: Thyroid tumors were collected from a series of 27 patients undergoing surgical excision of papillary and follicular thyroid tumors.Intervention: No intervention was conducted.Main Outcome Measure: The expression of PBF in thyroid cancers compared with normal thyroid, hypothesized before the investigation to be raised in tumors, was the main outcome measure.Results: PBF mRNA expression was higher in differentiated thyroid carcinomas than in normal thyroid (P < 0.001; n = 27) and was independently associated with tumor recurrence (P = 0.002; R-2 = 0.49). PTTG was able to up-regulate PBF mRNA expression in vitro (P < 0.001; n = 12), and stable overexpression of PBF in NIH3T3 cells resulted in significant colony formation (P < 0.001; n = 12). In vivo, stable sc overexpression of PBF induced tumor formation in athymic nude mice.Conclusions: PBF is an additional prognostic indicator in differentiated thyroid cancer that is transforming in vitro and tumorigenic in vivo.