Eszlinger Markus, Krohn Knut, Berger Kerstin, Läuter Jürgen, Kropf Siegfried, Beck Martin, Führer Dagmar, Paschke Ralf
III. Medical Department, University of Leipzig, Philipp-Rosenthal-Strasse 27, D-04103 Leipzig, Germany.
J Clin Endocrinol Metab. 2005 Feb;90(2):1163-70. doi: 10.1210/jc.2004-1242. Epub 2004 Nov 2.
In contrast to the molecular etiology of autonomously functioning thyroid nodules, the molecular cause of cold thyroid nodules (CTNs), their benign, functional inactive counterparts, are so far largely unknown. Because of the partially dedifferentiated phenotype of CTNs, alterations in signaling cascades that favor proliferation, but not differentiation, are likely candidates for tumor induction and progression. The importance of RAS mutations for the development of benign nodules with follicular histology is still in question. However, differentially expressed genes in the context of their signaling cascades could define aberrant signaling in CTNs. Therefore, we investigated gene expression in 22 CTNs and their normal surrounding tissue using Affymetrix GeneChips. Most prominently, data analysis revealed an increased expression of cell cycle-associated genes and a special relevance of protein kinase C signaling, whereas no evidence of RAS-MAPK signaling in CTNs was found. Moreover, we determined 31 differentially regulated genes in CTNs, including several histone mRNAs. Taken together, these results explain recent findings showing an increased proliferation in CTNs and draw attention to protein kinase C signaling, but away from RAS-MAPK signaling, as being involved in the etiology of CTNs.
与自主功能性甲状腺结节的分子病因不同，冷甲状腺结节（CTN）——良性、功能无活性的对应物——的分子病因目前在很大程度上仍不清楚。由于CTN存在部分去分化表型，有利于增殖而非分化的信号级联改变可能是肿瘤诱导和进展的候选因素。RAS突变对滤泡组织学良性结节发生发展的重要性仍存在疑问。然而，在其信号级联背景下差异表达的基因可能定义了CTN中的异常信号。因此，我们使用Affymetrix基因芯片研究了22个CTN及其正常周围组织中的基因表达。最显著的是，数据分析显示细胞周期相关基因表达增加以及蛋白激酶C信号具有特殊相关性，而未在CTN中发现RAS-MAPK信号的证据。此外，我们确定了CTN中31个差异调节基因，包括几个组蛋白mRNA。综上所述，这些结果解释了最近显示CTN增殖增加的研究发现，并将注意力引向参与CTN病因的蛋白激酶C信号，而非RAS-MAPK信号。
