Karger S, Berger K, Eszlinger M, Tannapfel A, Dralle H, Paschke R, Führer D
III. Medical Department, University of Leipzig, Leipzig, Germany.
Thyroid. 2005 Sep;15(9):997-1003. doi: 10.1089/thy.2005.15.997.
Impairment of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) function through a dominant negative PAX-8/PPAR-gamma fusion gene or other events resulting in wild-type PPAR-gamma downregulation has been implicated in malignant thyroid cell transformation. The aim of our study was to perform a systematic evaluation of PPAR-gamma mRNA and protein expression in normal thyroid tissue as opposed to benign thyroid pathologies of different functional status and thyroid malignancy, to gain further insights into a putative physiological role of PPAR-gamma in the thyroid and to define whether PPAR-gamma could serve as a marker of thyroid cell differentiation. Ten cold benign (CTN) and 10 toxic (TTN) thyroid nodules and corresponding normal thyroid tissues, 10 follicular thyroid cancers (FTC), 10 papillary thyroid cancers (PTC) and 8 Graves' disease (GD) thyroids were studied by real-time polymerase chain reaction (PCR), immunohistochemistry and reverse transcriptase (RT)-PCR (PAX-8/PPAR-gamma fusion gene). PPAR-gamma mRNA expression was demonstrated in all samples. When comparing benign nodular and normal thyroid tissue of the same patient no significant difference in PPAR-gamma mRNA expression was observed. PPAR-gamma mRNA levels were similar in CTN and FTC. In contrast, PPAR-gamma mRNA expression was downregulated in 9 of 10 PTC and all GD samples, whereby at least 4 fold downregulation (compared with normal and benign nodular thyroid tissues) was observed in the latter. Immunohistochemistry showed an increased, patchy PPAR-gamma nuclear staining in CTNs and TTNs and only faint staining in the corresponding normal thyroid tissues. A diffuse and weak PPAR-gamma staining pattern was observed in all GD samples. No PAX-8/PPAR-gamma rearrangements were detected in any of the 68 thyroid tissue samples. In conclusion PPAR-gamma mRNA and protein expression levels are not concordant in benign thyroid nodular disease. Furthermore there is no clear-cut association of PPAR-gamma mRNA expression with follicular thyroid tumorigenesis. Absence of a PAX-8/PPAR-gamma fusion gene in the series of 68 thyroid samples is in agreement with the suggestion of PAX-8/PPAR-gamma rearrangement being restricted to a subset of follicular thyroid cancers. The marked downregulation of PPAR-gamma in GD warrants further investigation and could be linked, for example, with changes in apoptosis.
通过显性负性PAX - 8/PPAR - γ融合基因或其他导致野生型PPAR - γ下调的事件引起的过氧化物酶体增殖物激活受体γ（PPAR - γ）功能受损，与甲状腺恶性细胞转化有关。我们研究的目的是对正常甲状腺组织、不同功能状态的良性甲状腺病变以及甲状腺恶性肿瘤中的PPAR - γ mRNA和蛋白表达进行系统评估，以进一步了解PPAR - γ在甲状腺中的假定生理作用，并确定PPAR - γ是否可作为甲状腺细胞分化的标志物。通过实时聚合酶链反应（PCR）、免疫组织化学和逆转录（RT）-PCR（检测PAX - 8/PPAR - γ融合基因）对10个冷良性（CTN）和10个毒性（TTN）甲状腺结节及相应的正常甲状腺组织、10个滤泡状甲状腺癌（FTC）、10个乳头状甲状腺癌（PTC）和8个格雷夫斯病（GD）甲状腺进行了研究。所有样本均检测到PPAR - γ mRNA表达。比较同一患者的良性结节性甲状腺组织和正常甲状腺组织时，未观察到PPAR - γ mRNA表达有显著差异。CTN和FTC中的PPAR - γ mRNA水平相似。相比之下，10个PTC样本中的9个以及所有GD样本中PPAR - γ mRNA表达下调，其中后者至少下调了4倍（与正常和良性结节性甲状腺组织相比）。免疫组织化学显示CTN和TTN中PPAR - γ核染色增加且呈斑片状，而相应的正常甲状腺组织中染色较淡。所有GD样本中均观察到弥漫性且较弱的PPAR - γ染色模式。在68个甲状腺组织样本中均未检测到PAX - 8/PPAR - γ重排。总之，在良性甲状腺结节性疾病中，PPAR - γ mRNA和蛋白表达水平不一致。此外，PPAR - γ mRNA表达与滤泡状甲状腺肿瘤发生之间没有明确的关联。68个甲状腺样本系列中未检测到PAX - 8/PPAR - γ融合基因，这与PAX - 8/PPAR - γ重排仅限于滤泡状甲状腺癌的一个亚组的观点一致。GD中PPAR - γ的显著下调值得进一步研究，例如可能与细胞凋亡的变化有关。
