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Shlomo Melmed - One of the best experts on this subject based on the ideXlab platform.
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Pituitary Tumour-transforming gene (PTTG) and Pituitary senescence.
Hormone Research in Paediatrics, 2009Co-Authors: Vera Chesnokova, Shlomo MelmedAbstract:Pituitary Tumours account for 15% of intracranial neoplasms and are benign monoclonal neoplasms that may be clinically silent or secrete hormones, including prolactin, growth hormone, adrenocorticotrophic hormone or, rarely, thyroid-stimulating hormone or gonadotrophins. These adenomas account for clinical infertility, growth disorders and hypercortisolism or metabolic dysfunctions associated with hypopituitarism. We explored the role of disordered Pituitary cell proliferation control in the pathogenesis of these invariably benign adenomas, studying the mechanisms underlying Pituitary aneuploidy, premature proliferative arrest (senescence), markers of cell proliferation and tumorigenesis in single, double or triply mutant transgenic mice with mutations of Rb, Pttg and/or p21. Our results provide further insights into the role of cell-cycle control and growth constraints on experimental and human Pituitary Tumours, which underlie their failure to progress to malignancy. These results improve our understanding of Pituitary syndromes associated with infertility, growth disorders, hypercortisolism or adrenal, thyroid and gonadal failure due to abrogated Pituitary function.
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expression and function of Pituitary Tumour transforming gene for t lymphocyte activation
British Journal of Haematology, 2002Co-Authors: Rostyslav Stoika, Shlomo MelmedAbstract:Pituitary Tumour transforming gene (PTTG) isolated from Pituitary Tumour cells transforms cells in vitro and causes in vivo Tumour formation. PTTG is expressed in several human Tumours and cell lines. In normal adult tissues, the testis expresses abundant levels of PTTG mRNA comparable to that found in Tumour cells. Although PTTG is not expressed in resting T cells, we showed here that activation of normal adult human T cells using either immobilized anti-CD3 antibodies or phytohaemagglutinin was accompanied by marked PTTG induction, reaching levels observed in human Tumour cells. Inhibitors of T-cell functions, such as cyclosporin A and hydrocortisone, decreased induction of PTTG mRNA expression. During T-cell activation, PTTG mRNA abundance corresponded with the increase in S-phase cells, suggesting PTTG involvement in cell cycle-dependent processes. These results showed that PTTG-1 expression follows cell cycling patterns in T lymphocytes, providing a convenient model for studying PTTG functions in normal cells.
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expression of Pituitary Tumour transforming gene in colorectal Tumours
The Lancet, 2000Co-Authors: Anthony P. Heaney, Regina Singson, Chris J Mccabe, Viera Nelson, Masahiro Nakashima, Shlomo MelmedAbstract:Summary Background Basic fibroblast growth factor promotes angiogenesis and mitogenesis in colon carcinomas. PituitaryTumour transforming gene ( PTTG 1 ) causes in-vitro and in-vivo transformation, regulates secretion of basic fibroblast growth factor, and inhibits chromatid separation. Most normal tissues show little or no PTTG 1 expression but cancer cells express the gene abundantly. We postulated that PTTG 1 expression in colorectal Tumours is related to Tumour invasiveness. Methods PTTG 1 gene and protein expression were assessed in 68 colorectal Tumours and compared with invasive characteristics, such as lymph-node invasion, evidence of metastases, Tumour vessel density, and expression of basic fibroblast growth factor. PTTG 1 expression is given in terms of the fold-increase over that in normal-adjacent colorectal tissue. Findings PTTG 1 was overexpressed in all of 48 colon carcinomas (median fold-increase 2·2 [IQR 1·8–3·3]) and in 19 of 20 colonic polyps (2·2 [1·6–3·1]) compared with normal colonic tissue. Invasion of surrounding lymph nodes was associated with higher PTTG 1 expression than in carcinomas limited to the bowel wall (3·4 [2·1–5·9] vs 1·9 [1·7–2·4], p=0·007), and higher PTTG 1 expression was seen in more vascular than in less vascular Tumours (2·6 [1·9–5·1] vs 1·9 [1·8–2·5], p=0·04). Interpretation Increased Tumour PTTG 1 expression may be a marker of invasive colorectal carcinoma and could represent a new therapeutic target.
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Pituitary Tumour transforming gene: a novel factor in Pituitary Tumour formation.
Best Practice & Research Clinical Endocrinology & Metabolism, 1999Co-Authors: Anthony P. Heaney, Shlomo MelmedAbstract:Although Pituitary Tumours are common monoclonal neoplasms, they rarely metastasize outside the Pituitary fossa, even though they cause considerable morbidity and mortality. Many molecular events underlying Pituitary Tumourigenesis have been elucidated in recent years, but no clear Tumour marker has emerged that assists clinical decision-making with regard to appropriate therapy. Activating mutations and a loss of inactivating mutations, together with hypothalamic hormones, circulating hormones, growth factors and cytokines, co-operatively ensure the inexorable expansion of the initial mutated Pituitary cell clone. We have recently described a novel oestrogen-regulated activating oncogene, Pituitary Tumour transforming gene (PTTG), which is potently transforming in vitro and in vivo, regulates basic fibroblast growth factor secretion and inhibits chromatid separation. In experimental animal Pituitary Tumour models, increased PTTG expression occurs early in cell transformation (from normal to hyperplastic cell), PTTG overexpression being observed in 99% of Pituitary Tumours. PTTG presents an attractive target for designing subcellular Pituitary Tumour therapy, and an increased understanding of its role and that of other genetic events in Pituitary tumorigenesis may provide novel approaches to Pituitary Tumour management.
Christopher Mccabe - One of the best experts on this subject based on the ideXlab platform.
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Pituitary Tumour transforming gene pttg induces genetic instability in thyroid cells
Oncogene, 2005Co-Authors: Dae Kim, H Pemberton, Anna L Stratford, Kristien Buelaert, John Watkinson, Victor Lopes, J A Franklyn, Christopher MccabeAbstract:Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Cytogenetic studies have demonstrated the importance of aneuploidy in differentiated thyroid cancer development. The Pituitary Tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and overexpression of PTTG induces aneuploidy in vitro. Using fluorescent intersimple sequence repeat PCR (FISSR-PCR), we investigated the relationship between PTTG expression and the degree of genetic instability in normal and tumorous thyroid samples. The genomic instability index (GI index) was 6.7–72.7% higher in cancers than normal thyroid tissues. Follicular thyroid Tumours exhibited greater genetic instability than papillary Tumours (27.6% (n=9) versus 14.5% (n=10), P=0.03). We also demonstrated a strong relationship between PTTG expression and the degree of genetic instability in thyroid cancers (R2=0.80, P=0.007). To further investigate PTTG's role in genetic instability, we transfected FTC133 thyroid follicular cells and observed increased genetic instability in cells overexpressing PTTG compared with vector-only-transfected controls (n=3, GI Index VO=29.7±5.2 versus PTTG=63.7±6.4, P=0.013). Further, we observed a dose response in genetic instability and PTTG expression (GI Index low dose (0.5 μg DNA/ six-well plate) PTTG=15.3%±1.7 versus high dose (3 μg DNA) PTTG=50.8%±3.3, P=0.006). Overall, we describe the first use of FISSR-PCR in human cancers, and demonstrate that PTTG expression correlates with genetic instability in vivo, and induces genetic instability in vitro. We conclude that PTTG may be an important gene in the mutator phenotype development in thyroid cancer.
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expression of Pituitary Tumour transforming gene pttg and fibroblast growth factor 2 fgf 2 in human Pituitary adenomas relationships to clinical Tumour behaviour
Clinical Endocrinology, 2003Co-Authors: Christopher Mccabe, Anthony P. Heaney, J S Khaira, Kristien Boelaert, L Tannahill, S Hussain, Rosalind Mitchell, J Olliff, M C Sheppard, J A FranklynAbstract:Summary objective Pituitary Tumour transforming gene (PTTG) encodes a multifunctional protein that is implicated in initiating and perpetuating Pituitary adenoma growth. PTTG appears to have key regulatory functions in determining control of many fundamental cellular events including mitosis, cell transformation, DNA repair and gene regulation. Several of these events are mediated through interactions with PTTG binding factor (PBF) and fibroblast growth factor-2 (FGF-2). Given this background, we have determined the expression of PTTG, PBF, FGF-2 and its receptor FGF-R-1 in a large cohort of Pituitary adenomas and have sought associations between levels of gene expression and clinical markers of Tumour behaviour. patients and methods We used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses to measure PTTG, PBF, FGF-2 and FGF-R-1 expression in ex vivo Pituitary Tumours (N = 121). Clinical data, including accurate radiological assessment of Tumour characteristics, were used to determine any associations between gene expression and Tumour behaviour. results PTTG was increased significantly (fivefold, P = 0·005) in adenomas compared with normal pituitaries. We also demonstrated that PBF was similarly raised in adenomas (sixfold, P = 0·0001), and was significantly correlated with PTTG expression. FGF-2 and its receptor FGF-R-1 were also raised in adenomas compared with normal Pituitary tissue. Moreover, significantly enhanced expression of FGF-R-1 was observed in invasive adenomas compared with other Pituitary Tumours. conclusions Our data support a fundamental role for PTTG-mediated upregulation of FGF-2 signalling in Pituitary tumorigenesis and growth, and suggest that receptor-mediated mechanisms of growth factor action may be critically important. Further prospective studies are required to determine whether measurement of FGF-R-1 mRNA will be of clinical use as a prognostic marker in patients with Pituitary adenomas.
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PTTG--a new Pituitary Tumour transforming gene.
The Journal of endocrinology, 1999Co-Authors: Christopher Mccabe, N. J. L. GittoesAbstract:The pathogenesis of sporadic Pituitary Tumours remains elusive. Recently, a new candidate gene has been described which is able to induce Pituitary cell transformation, and the expression of which appears to be strongly correlated with Pituitary tumorigenesis. The so-called Pituitary Tumour transforming gene (PTTG) encodes a 23 kDa, 202 amino acid protein, and is located on chromosome 5q33, a locus previously associated with recurrent lung cancer and acute myelogenous leukaemias. Although the precise function of PTTG protein is unknown, in vitro experiments have demonstrated that it is capable of inducing fibroblast growth factor (FGF) expression. Mutation of the two proline-rich domains of the PTTG protein has also been shown to abolish subsequent FGF induction. Furthermore, in patients with Pituitary adenomas, serum FGF concentrations fall post-operatively after successful excision of the Tumour.
Anthony P. Heaney - One of the best experts on this subject based on the ideXlab platform.
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Pituitary Tumour pathogenesis
British Medical Bulletin, 2006Co-Authors: Anthony P. HeaneyAbstract:Pituitary adenomas are the most common Tumours in the central nervous system, make up approximately 10% of all primary intracerebral Tumours [1] and are found incidentally in 3-27% of autopsies [2]. The predisposition to Tumour formation of the highly specialized cellular phenotypes that characterize the anterior Pituitary is unexplained, but it is tempting to speculate that the same hormones, growth factors and cytokines derived from intra- and extra-Pituitary sites that maintain tight hypothalamic Pituitary control may also contribute to pituicyte transformation. The interplay between genetic and humoural factors to promote cellular transformation is exemplified in Pituitary tumorigenesis and is discussed in this review.
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expression of Pituitary Tumour transforming gene pttg and fibroblast growth factor 2 fgf 2 in human Pituitary adenomas relationships to clinical Tumour behaviour
Clinical Endocrinology, 2003Co-Authors: Christopher Mccabe, Anthony P. Heaney, J S Khaira, Kristien Boelaert, L Tannahill, S Hussain, Rosalind Mitchell, J Olliff, M C Sheppard, J A FranklynAbstract:Summary objective Pituitary Tumour transforming gene (PTTG) encodes a multifunctional protein that is implicated in initiating and perpetuating Pituitary adenoma growth. PTTG appears to have key regulatory functions in determining control of many fundamental cellular events including mitosis, cell transformation, DNA repair and gene regulation. Several of these events are mediated through interactions with PTTG binding factor (PBF) and fibroblast growth factor-2 (FGF-2). Given this background, we have determined the expression of PTTG, PBF, FGF-2 and its receptor FGF-R-1 in a large cohort of Pituitary adenomas and have sought associations between levels of gene expression and clinical markers of Tumour behaviour. patients and methods We used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses to measure PTTG, PBF, FGF-2 and FGF-R-1 expression in ex vivo Pituitary Tumours (N = 121). Clinical data, including accurate radiological assessment of Tumour characteristics, were used to determine any associations between gene expression and Tumour behaviour. results PTTG was increased significantly (fivefold, P = 0·005) in adenomas compared with normal pituitaries. We also demonstrated that PBF was similarly raised in adenomas (sixfold, P = 0·0001), and was significantly correlated with PTTG expression. FGF-2 and its receptor FGF-R-1 were also raised in adenomas compared with normal Pituitary tissue. Moreover, significantly enhanced expression of FGF-R-1 was observed in invasive adenomas compared with other Pituitary Tumours. conclusions Our data support a fundamental role for PTTG-mediated upregulation of FGF-2 signalling in Pituitary tumorigenesis and growth, and suggest that receptor-mediated mechanisms of growth factor action may be critically important. Further prospective studies are required to determine whether measurement of FGF-R-1 mRNA will be of clinical use as a prognostic marker in patients with Pituitary adenomas.
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expression of Pituitary Tumour transforming gene in colorectal Tumours
The Lancet, 2000Co-Authors: Anthony P. Heaney, Regina Singson, Chris J Mccabe, Viera Nelson, Masahiro Nakashima, Shlomo MelmedAbstract:Summary Background Basic fibroblast growth factor promotes angiogenesis and mitogenesis in colon carcinomas. PituitaryTumour transforming gene ( PTTG 1 ) causes in-vitro and in-vivo transformation, regulates secretion of basic fibroblast growth factor, and inhibits chromatid separation. Most normal tissues show little or no PTTG 1 expression but cancer cells express the gene abundantly. We postulated that PTTG 1 expression in colorectal Tumours is related to Tumour invasiveness. Methods PTTG 1 gene and protein expression were assessed in 68 colorectal Tumours and compared with invasive characteristics, such as lymph-node invasion, evidence of metastases, Tumour vessel density, and expression of basic fibroblast growth factor. PTTG 1 expression is given in terms of the fold-increase over that in normal-adjacent colorectal tissue. Findings PTTG 1 was overexpressed in all of 48 colon carcinomas (median fold-increase 2·2 [IQR 1·8–3·3]) and in 19 of 20 colonic polyps (2·2 [1·6–3·1]) compared with normal colonic tissue. Invasion of surrounding lymph nodes was associated with higher PTTG 1 expression than in carcinomas limited to the bowel wall (3·4 [2·1–5·9] vs 1·9 [1·7–2·4], p=0·007), and higher PTTG 1 expression was seen in more vascular than in less vascular Tumours (2·6 [1·9–5·1] vs 1·9 [1·8–2·5], p=0·04). Interpretation Increased Tumour PTTG 1 expression may be a marker of invasive colorectal carcinoma and could represent a new therapeutic target.
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Pituitary Tumour transforming gene: a novel factor in Pituitary Tumour formation.
Best Practice & Research Clinical Endocrinology & Metabolism, 1999Co-Authors: Anthony P. Heaney, Shlomo MelmedAbstract:Although Pituitary Tumours are common monoclonal neoplasms, they rarely metastasize outside the Pituitary fossa, even though they cause considerable morbidity and mortality. Many molecular events underlying Pituitary Tumourigenesis have been elucidated in recent years, but no clear Tumour marker has emerged that assists clinical decision-making with regard to appropriate therapy. Activating mutations and a loss of inactivating mutations, together with hypothalamic hormones, circulating hormones, growth factors and cytokines, co-operatively ensure the inexorable expansion of the initial mutated Pituitary cell clone. We have recently described a novel oestrogen-regulated activating oncogene, Pituitary Tumour transforming gene (PTTG), which is potently transforming in vitro and in vivo, regulates basic fibroblast growth factor secretion and inhibits chromatid separation. In experimental animal Pituitary Tumour models, increased PTTG expression occurs early in cell transformation (from normal to hyperplastic cell), PTTG overexpression being observed in 99% of Pituitary Tumours. PTTG presents an attractive target for designing subcellular Pituitary Tumour therapy, and an increased understanding of its role and that of other genetic events in Pituitary tumorigenesis may provide novel approaches to Pituitary Tumour management.
Eduardo Arzt - One of the best experts on this subject based on the ideXlab platform.
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curcumin suppresses hif1a synthesis and vegfa release in Pituitary adenomas
Journal of Endocrinology, 2012Co-Authors: Bing Shan, C Schaaf, Anne Schmidt, Kristin Lucia, Michael Buchfelder, Marco Losa, Dominique Kuhlen, Jurgen Kreutzer, Marcelo J Perone, Eduardo ArztAbstract:Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plant Curcuma longa, displays multiple actions on solid Tumours including anti-angiogenic effects. Here we have studied in rodent and human Pituitary Tumour cells the influence of curcumin on the production of hypoxia inducible factor 1a (HIF1A) and vascular endothelial growth factor A (VEGFA), two key components involved in Tumour neovascularisation through angiogenesis. Curcumin dose-dependently inhibited basal VEGFA secretion in corticotroph AtT20 mouse and lactosomatotroph GH3 rat Pituitary Tumour cells as well as in all human Pituitary adenoma cell cultures (nZ32) studied. Under hypoxia-mimicking conditions (CoCl2 treatment) in AtT20 and GH3 cells as well as in all human Pituitary adenoma cell cultures (nZ8) studied, curcumin strongly suppressed the induction of mRNA synthesis and protein production of HIF1A, the regulated subunit of the hypoxia-induced transcription factor HIF1. Curcumin also blocked hypoxiainduced mRNA synthesis and secretion of VEGFA in GH3 cells and in all human Pituitary adenoma cell cultures investigated (nZ18). Thus, curcumin may inhibit Pituitary adenoma progression not only through previously demonstrated antiproliferative and pro-apoptotic actions but also by its suppressive effects on Pituitary Tumour neovascularisation.
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rsume is implicated in hif 1 induced vegf a production in Pituitary Tumour cells
Endocrine-related Cancer, 2012Co-Authors: Bing Shan, Michael Buchfelder, Marco Losa, Eduardo Arzt, Juan Gerez, Mariana Haedo, Mariana Fuertes, Marily Theodoropoulou, Gunter K Stalla, U RennerAbstract:The recently cloned small RWD-domain containing protein RSUME was shown to increase protein levels of hypoxia-inducible factor-1α (HIF-1α). The latter is the oxygen-regulated subunit of HIF-1, the most important transcription factor of the cellular adaptive processes to hypoxic conditions. It is also a major regulator of vascular endothelial growth factor-A (VEGF-A), which is critically involved in the complex process of Tumour neovascularisation. In this study, the expression and role of RSUME in Pituitary Tumours was studied. We found that RSUME mRNA was up-regulated in Pituitary adenomas and significantly correlated with HIF-1α mRNA levels. Hypoxia (1% O(2)) or treatment with hypoxia-mimicking CoCl(2) enhanced RSUME and HIF-1α expression, induced translocation of HIF-1α to the nuclei and stimulated VEGF-A production both in Pituitary Tumour cell lines and primary human Pituitary adenoma cell cultures. When RSUME expression was specifically down-regulated by siRNA, the CoCl(2)-induced increase VEGF-A secretion was strongly reduced which was shown to be a consequence of the RSUME knockdown-associated reduction of HIF-1α synthesis. Thus, RSUME plays an important role in initiating Pituitary Tumour neovascularisation through regulating HIF-1α levels and subsequent VEGF-A production and may therefore be critically involved in Pituitary adenoma progression.
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curcumin acts as anti tumorigenic and hormone suppressive agent in murine and human Pituitary Tumour cells in vitro and in vivo
Endocrine-related Cancer, 2009Co-Authors: C Schaaf, Bing Shan, Michael Buchfelder, Marco Losa, Eduardo Arzt, Gunter K Stalla, J Kreutzer, Walter Rachinger, Tobias Schilling, Marcelo J PeroneAbstract:Curcumin (diferuloylmethane) is the active ingredient of the spice plant Curcuma longa and has been shown to act anti-tumorigenic in different types of Tumours. Therefore, we have studied its effect in Pituitary Tumour cell lines and adenomas. Proliferation of lactosomatotroph GH3 and somatotroph MtT/S rat Pituitary cells as well as of corticotroph AtT20 mouse Pituitary cells was inhibited by curcumin in monolayer cell culture and in colony formation assay in soft agar. Fluorescence-activated cell sorting (FACS) analysis demonstrated curcumin-induced cell cycle arrest at G2/M. Analysis of cell cycle proteins by immunoblotting showed reduction in cyclin D(1), cyclin-dependent kinase 4 and no change in p27(kip). FACS analysis with Annexin V-FITC/7-aminoactinomycin D staining demonstrated curcumin-induced early apoptosis after 3, 6, 12 and 24 h treatment and nearly no necrosis. Induction of DNA fragmentation, reduction of Bcl-2 and enhancement of cleaved caspase-3 further confirmed induction of apoptosis by curcumin. Growth of GH3 Tumours in athymic nude mice was suppressed by curcumin in vivo. In endocrine Pituitary Tumour cell lines, GH, ACTH and prolactin production were inhibited by curcumin. Studies in 25 human Pituitary adenoma cell cultures have confirmed the anti-tumorigenic and hormone-suppressive effects of curcumin. Altogether, the results described in this report suggest this natural compound as a good candidate for therapeutic use on Pituitary Tumours.
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bacterial endotoxin lipopolysaccharide stimulates interleukin 6 production and inhibits growth of Pituitary Tumour cells expressing the toll like receptor 4
Journal of Neuroendocrinology, 2005Co-Authors: M Tichomirowa, Marco Losa, Eduardo Arzt, Marily Theodoropoulou, G K Stalla, P Lohrer, Ludwig Schaaf, Eberhard Uhl, M Lange, U RennerAbstract:Members of the Toll receptor (Tlr) family have a crucial role in the innate immune response following bacterial infection. The effects of Gram-negative bacteria-derived endotoxins (lipopolysaccharide, LPS) are predominantly mediated by Tlr4, and we have recently shown that Pituitary folliculostellate cells express functional Tlr4. In the present study, we investigated whether Tlr4 is also present in normal and transformed endocrine epithelial Pituitary cell types. By reverse transcriptase-polymerase chain reaction, Tlr4 mRNA expression was found in some Pituitary epithelial Tumour cell lines (AtT20, HP75), whereas others were negative (GH3, αT3-1). Tlr4 protein was detected by immunohistochemistry in a few epithelial cells in normal human anterior pituitaries and in 26 out of 67 human Pituitary Tumours analysed. LPS had no effect on adrenocorticotropic hormone secretion in Tlr4-positive AtT20 cells, but it suppressed the growth of these cells in a dose-dependent manner. As expected, neither hormone secretion, nor growth of Tlr4-negative GH3 cells was affected by LPS. In cell cultures of Tlr4-positive Pituitary adenomas, LPS dose-dependently stimulated the production of interleukin (IL)-6, which is known to induce growth and hormone production in Pituitary Tumours. The LPS-induced IL-6 production was blocked by the specific p38αMAP kinase inhibitor, SB203580, and by the synthetic glucocorticoid, dexamethasone. The data suggest that, during Gram-negative bacteria-induced infections or inflammatory processes, LPS could affect Pituitary Tumour pathophysiology and progression in the subset of Tlr4-expressing Pituitary adenomas.
J M Burrin - One of the best experts on this subject based on the ideXlab platform.
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the relationship between Pituitary Tumour transforming gene pttg expression and in vitro hormone and vascular endothelial growth factor vegf secretion from human Pituitary adenomas
European Journal of Endocrinology, 2003Co-Authors: J A C Hunter, Jane Evanson, G M Besser, J P Monson, R H Skelly, Simon Aylwin, J F Geddes, J M BurrinAbstract: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 ðP , 0:01; ANOVAÞ: A positive correlation was demonstrated between PTTG expression and in vitro GH secretion ðr ¼ 0:41; P , 0:01; SpearmanÞ 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.