Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour
| Autor: | C J, McCabe, J S, Khaira, K, Boelaert, A P, Heaney, L A, Tannahill, S, Hussain, R, Mitchell, J, Olliff, M C, Sheppard, J A, Franklyn, N J L, Gittoes |
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| Rok vydání: | 2003 |
| Předmět: |
Adenoma
Adult Male Chi-Square Distribution Reverse Transcriptase Polymerase Chain Reaction Blotting Western Intracellular Signaling Peptides and Proteins Gene Expression Membrane Proteins Receptor Protein-Tyrosine Kinases Middle Aged Magnetic Resonance Imaging Receptors Fibroblast Growth Factor Statistics Nonparametric Neoplasm Proteins Cohort Studies DNA-Binding Proteins Securin Biomarkers Tumor Humans Female Fibroblast Growth Factor 2 Pituitary Neoplasms RNA Messenger Receptor Fibroblast Growth Factor Type 1 |
| Zdroj: | Clinical endocrinology. 58(2) |
| ISSN: | 0300-0664 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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