The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas

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.