Capital Medical University, Beijing 100069, China.
Chin Med J (Engl). 2010 Dec;123(23):3455-61.
Adrenocorticotrophin (ACTH)-secreting pituitary adenomas account for approximately 7% - 14% of all pituitary adenomas, but its pathogenesis is still enigmatic. This study aimed to explore mechanisms underlying the pathogenesis of ACTH-secreting pituitary adenomas.
We used fiber-optic beadarray to examine gene expression in three ACTH-secreting adenomas compared with three normal pituitaries. Four differentially expressed genes from the three ACTH-secreting adenomas and three normal pituitaries were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction (RT-qPCR). We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.
Fiber-optic beadarray analysis showed that the expression of 28 genes and 8 expressed sequence tags (ESTs) were significantly increased and the expression of 412 genes and 31 ESTs were significantly decreased. Bioinformatic and pathway analysis showed that the genes HIGD1B, EPS8, HPGD, DAPK2, and IGFBP3 and the transforming growth factor (TGF)-β signaling pathway and extracellular matrix (ECM)-receptor interaction pathway may play important roles in tumorigenesis and progression of ACTH-secreting pituitary adenomas.
Our data suggest that numerous aberrantly expressed genes and several pathways are involved in the pathogenesis of ACTH-secreting pituitary adenomas. Fiber-optic beadarray combined with pathway analysis of differential gene expression appears to be a valid method of investigating tumour pathogenesis.
促肾上腺皮质激素(ACTH)分泌性垂体腺瘤约占所有垂体腺瘤的 7%-14%,但其发病机制仍不清楚。本研究旨在探讨 ACTH 分泌性垂体腺瘤发病机制。
我们使用光纤珠阵列比较了三例 ACTH 分泌性腺瘤与三例正常垂体的基因表达。从三例 ACTH 分泌性腺瘤和三例正常垂体中随机选择四个差异表达基因,通过逆转录实时定量聚合酶链反应(RT-qPCR)进行验证。然后,我们分析了差异表达基因谱与京都基因与基因组百科全书(KEGG)途径。
光纤珠阵列分析显示,28 个基因和 8 个表达序列标签(ESTs)的表达明显增加,412 个基因和 31 个 ESTs 的表达明显降低。生物信息学和通路分析表明,基因 HIGD1B、EPS8、HPGD、DAPK2 和 IGFBP3 以及转化生长因子(TGF)-β信号通路和细胞外基质(ECM)-受体相互作用通路可能在 ACTH 分泌性垂体腺瘤的发生和进展中发挥重要作用。
我们的数据表明,许多异常表达的基因和几个通路参与了 ACTH 分泌性垂体腺瘤的发病机制。光纤珠阵列结合差异基因表达的通路分析似乎是一种有效的肿瘤发病机制研究方法。