The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas
The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas
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DOI：
10.1530/eje.0.1480203
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发表时间：
2003-02-01
影响因子：
5.8
通讯作者：
Burrin, JM
中科院分区：
文献类型：
--
作者：
Hunter, JAC;Skelly, RH;Burrin, JM
目的：垂体肿瘤转化基因（PTTG）是最近发现的一个原癌基因，在垂体肿瘤中广泛表达，其表达水平高于正常垂体。虽然PTTG蛋白的确切功能尚不清楚，但体外实验表明它诱导血管生成。在这项研究中，我们研究了PTTG表达水平与肿瘤表型、肿瘤大小、体外垂体激素分泌和血管内皮生长因子（VEGF）（一种有效的血管生成因子）释放之间的潜在关系。垂体瘤（12个生长激素细胞，5个催乳细胞，5个促肾上腺皮质激素细胞和18个无功能细胞）通过细胞培养进行了研究，体外测定垂体前叶激素和VEGF的基础分泌。免疫细胞化学方法用于临床诊断和肿瘤表型的确认。比较RT-PCR检测PTTG mRNA表达。结果：PTTG表达在生长激素肿瘤中是无功能腺瘤的2.7倍（P < 0.01，ANOVA）。PTTG表达与GH分泌呈正相关（r = 0.41，P < 0.01，斯皮尔曼），但与其他垂体激素无相关性。在40例垂体瘤中的16例中，我们能够确定VEGF的体外分泌，并将其与PTTG表达相关。所有检测的腺瘤都分泌可测量的VEGF，但分泌的VEGF量与肿瘤表型或PTTG表达之间没有相关性。无论是PTTG的表达，也不VEGF的分泌与肿瘤volume.Conclusions：我们的研究已经证实了PTTG在垂体腺瘤的存在，并表现出更高的水平在生长激素肿瘤的表达和GH分泌的显着相关性。我们未能证明PTTG表达和血管生成因子的产生之间的关系。VEGF或肿瘤体积。因此，虽然PTTG诱导血管生成实验，它似乎不太可能是一个VEGF介导的血管生成机制发生在垂体肿瘤的进展。
Objective: Pituitary tumour transforming gene (PTTG) is a recently identified protooncogene, ubiquitously expressed in pituitary tumours at levels higher than those detected in normal pituitary. Although the precise function of PTTG protein is unknown, in vitro experiments have shown that it induces angiogenesis. In this study, we have examined the potential relationship between the level of PTTG expression and tumour phenotype, tumour size, in vitro pituitary hormone secretion and release of vascular endothelial growth factor (VEGF), a potent angiogenic factor.Methods: Pituitary tumours (12 somatotroph, five lactotroph, five corticotroph and 18 non-functioning) were studied by cell culture, measuring the basal secretion of anterior pituitary hormones and VEGF in vitro. Immunocytochemistry was used to confirm the clinical diagnosis and tumour phenotype. PTTG mRNA expression was investigated by comparative RT-PCR. Tumour volume was quantitated from pre-operative MRI scans.Results: PTTG expression was significantly increased 2.7-fold in somatotroph tumours compared with non-functioning adenomas (P < 0.01, ANOVA). A positive correlation was demonstrated between PTTG expression and in vitro GH secretion (r = 0.41, P < 0.01, Spearman) but no correlations were found for any of the other pituitary hormones. In 16 out of 40 pituitary tumours, we were able to determine the in vitro secretion of VEGF and relate this to PTTG expression. All of the adenomas tested secreted measurable VEGF but there was no correlation between the amount of VEGF secreted and either the tumour phenotype or PTTG expression. Neither PTTG expression nor VEGF secretion correlated with tumour volume.Conclusions: Our studies have confirmed the presence of PTTG in pituitary adenomas and demonstrated a higher level of expression in somatotroph tumours and a significant correlation with GH secretion. We failed to demonstrate a relationship between PTTG expression and production of the angiogenic factor. VEGF or tumour volume. Thus, although PTTG induces angiogenesis experimentally, it seems unlikely that a VEGF-mediated angiogenic mechanism occurs during pituitary tumour progression.