Molecular pathogenesis of human prolactinomas identified by gene expression profiling, RT-qPCR, and proteomic analyses
Molecular pathogenesis of human prolactinomas identified by gene expression profiling, RT-qPCR, and proteomic analyses
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DOI：
10.1007/s11102-007-0082-2
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发表时间：
2008-09-01
期刊：
影响因子：
3.8
通讯作者：
Oyesiku, Nelson M.
中科院分区：
文献类型：
--
作者：
Evans, Chheng-Orn;Moreno, Carlos S.;Oyesiku, Nelson M.
催乳素瘤的分子发病机制一直难以阐明;除了在单个侵袭性催乳素瘤中的RAS突变外，未发现突变变化。在催乳素瘤中，另一个障碍是缺乏适合分子分析的手术标本，因为由于药物治疗的可用性和有效性，催乳素瘤很少被切除。在没有突变事件的情况下，已经寻找并检测到基因表达变化。使用高通量分析，从一个大的银行的人垂体腺瘤，我们检查这些肿瘤，根据他们的分子概况，而不是传统的免疫组化。我们研究了6个泌乳素瘤和8个正常垂体腺使用寡核苷酸基因芯片，逆转录-实时定量聚合酶链反应，使用10个泌乳素瘤，和蛋白质组学分析，以检查蛋白质表达在4个泌乳素瘤。微阵列分析确定了726个独特的基因，这些基因在泌乳素瘤和正常腺体之间具有统计学显著差异，而蛋白质组学分析确定了4种不同的上调和19种下调蛋白质。在泌乳素瘤中，Notch通路的几个组成部分发生了改变，Pit-1转录因子和生存因子BAG 1的表达增加，但E-钙粘蛋白和N-钙粘蛋白的表达减少。两者合计，表达谱和蛋白质组学分析已经确定了独特的催乳素瘤，可能有助于其发病机制的分子特征。在当今的分子医学时代，这些发现大大提高了我们的理解和取代免疫组化诊断。
The molecular pathogenesis of prolactinomas has resisted elucidation; with the exception of a RAS mutation in a single aggressive prolactinoma, no mutational changes have been identified. In prolactinomas, a further obstacle has been the paucity of surgical specimens suitable for molecular analysis since prolactionomas are infrequently removed due to the availability and effectiveness of medical therapy. In the absence of mutational events, gene expression changes have been sought and detected. Using high-throughput analysis from a large bank of human pituitary adenomas, we examined these tumors according to their molecular profiles rather than traditional immunohistochemistry. We examined six prolactinomas and eight normal pituitary glands using oligonucleotide GeneChip microarrays, reverse transcription-real time quantitative polymerase chain reaction using 10 prolactinomas, and proteomic analysis to examine protein expression in four prolactinomas. Microarray analyses identified 726 unique genes that were statistically significantly different between prolactinomas and normal glands, whereas proteomic analysis identified four differently up-regulated and 19 down-regulated proteins. Several components of the Notch pathway were altered in prolactinomas, and there was an increased expression of the Pit-1 transcription factor, and the survival factor BAG1 but decreased E-cadherin and N-cadherin expression. Taken together, expression profiling and proteomic analyses have identified molecular features unique to prolactinomas that may contribute to their pathogenesis. In the current era of molecular medicine, these findings greatly enhance our understanding and supercede immunohistochemical diagnosis.