Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia.
Pancreas. 2010 Nov;39(8):1140-6. doi: 10.1097/MPA.0b013e3181dc67fc.
To identify gene expression alterations associated with insulinoma formation and progression in 2 mouse models of multiple endocrine neoplasia type 1.
Mice were killed at 12 or 16 months, and pancreatic islets were isolated by enzymatic and physical disruption. Islets were separated by size representing control, normal, hyperplastic, and adenomous islets. RNA was isolated from these islets and profiled on Sentrix Mouse-6 Expression version 1 BeadChips. Array data were analyzed in GeneSpring.
One hundred and one genes that were significantly (P ≤ 0.05) altered in hyperplastic islets and insulinomas compared with normal islets were identified. Of these, 64 gene elements showed reduced messenger RNA levels and 37 gene elements had increased gene expression compared with control islets. Altered expression of 3 genes, namely, Gata6, Tspan8, and s100a8, was confirmed by quantitative reverse transcription-polymerase chain reaction, and aberrant levels of Tspan8 and Lmo2 protein measured by Western blot correlated with the changes in messenger RNA levels.
These results suggest that alterations in gene expression of Gata6, Tspan8, S100a8, and Lmo2 may act via novel pathways that play functionally important roles in Men1-associated tumor progression.
在多发性内分泌肿瘤 1 型的 2 种小鼠模型中，鉴定与胰岛素瘤形成和进展相关的基因表达改变。
小鼠在 12 或 16 个月时处死，通过酶和物理破坏分离胰岛。胰岛按大小分离，代表对照、正常、增生和腺瘤胰岛。从这些胰岛中分离 RNA，并在 Sentrix Mouse-6 Expression version 1 BeadChips 上进行分析。在 GeneSpring 中分析阵列数据。
与正常胰岛相比，在增生胰岛和胰岛素瘤中发现了 101 个明显（P ≤ 0.05）改变的基因。其中，64 个基因元件的信使 RNA 水平降低，37 个基因元件的基因表达增加。通过定量逆转录聚合酶链反应证实了 3 个基因（Gata6、Tspan8 和 s100a8）的表达改变，Western blot 测量的 Tspan8 和 Lmo2 蛋白异常水平与信使 RNA 水平的变化相关。
这些结果表明，Gata6、Tspan8、S100a8 和 Lmo2 的基因表达改变可能通过新的途径发挥作用，在 Men1 相关肿瘤进展中发挥重要功能作用。
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