Expression Analysis of GADD45γ, MEG3, and p8 in Pituitary Adenomas
Expression Analysis of GADD45γ, MEG3, and p8 in Pituitary Adenomas
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DOI：
10.1055/s-0034-1383566
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发表时间：
2014-08-01
影响因子：
2.2
通讯作者：
Petersenn, S.
中科院分区：
文献类型：
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作者：
Binse, I.;Ueberberg, B.;Petersenn, S.
以往的研究表明，GADD45-GAMA、MEG3和P8基因的异常表达水平而不是基因改变可能在垂体腺瘤的发病机制中起作用。我们分析了它们在不同的正常人体组织和不同类型的垂体瘤中的表达，并研究了腺瘤中的GADD45伽玛突变。应用实时荧光定量RT-PCR技术对24例正常组织、34例无功能组织、24例促生长激素细胞、12例促肾上腺皮质激素腺瘤、4例催乳素瘤、1例FSH瘤和6例正常脑垂体进行了绝对定量。此外，我们还研究了临床数据和基因表达之间的关系。通过单链构象多态分析(SSCP)和测序筛选GADD45伽玛突变亚群。所有正常人组织均表达GADD45-γ、MEG3和p8基因。GADD45γ在无功能腺瘤中的表达水平显著低于正常垂体腺瘤和生长激素腺瘤。P8和MEG3在无功能腺瘤和促肾上腺皮质激素腺瘤中的表达水平显著低于正常垂体。GADD45-γ在女性垂体腺瘤中的表达显著高于女性患者。未发现GADD45伽马基因突变。GADD45伽马、MEG3和p8似乎在人体各种组织中具有生理功能。GADD45γ、MEG3和P8可能参与了无功能和促肾上腺皮质激素垂体瘤的发病机制。女性似乎倾向于在垂体腺瘤中略高表达GADD45。GADD45伽马基因突变不太可能参与垂体腺瘤的发病。
Preceding studies have indicated that aberrant expression levels rather than genetic changes of GADD45 gamma, MEG3, and p8 gene might play a role in the pathogenesis of pituitary adenomas. We analysed their expression in various normal human tissues and in different pituitary tumour types, and investigated GADD45 gamma mutations in a subset of adenomas. Absolute quantification by real-time RT-PCR was performed in 24 normal tissues as well as in 34 nonfunctioning, 24 somatotroph, 12 corticotroph adenomas, 4 prolactinomas, 1 FSHoma, and in 6 normal pituitaries. Furthermore, we investigated the relationship between clinical data and gene expression. A subset was screened for GADD45 gamma mutations by single strand conformation polymorphism analysis (SSCP) and sequencing. All normal human tissues expressed GADD45 gamma, MEG3, and p8 mRNA. For GADD45 gamma, significantly lower expression levels were found in nonfunctioning adenomas compared with normal pituitary and somatotroph adenomas. P8 and MEG3 mRNA levels were significantly lower in nonfunctioning and corticotroph adenomas compared with normal pituitary. Expression of GADD45 gamma was significantly higher in pituitary adenomas of female patients. No mutation was found in the GADD45 gamma gene. GADD45 gamma, MEG3, and p8 appear to have physiological functions in a variety of human tissues. GADD45 gamma, MEG3, and P8 may be involved in the pathogenesis of nonfunctioning and corticotroph pituitary tumours. Female gender seems to predispose to slightly higher GADD45 gamma expression in pituitary adenomas. Mutations of the GADD45 gamma are unlikely to be involved in the pathogenesis of pituitary adenomas.