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Title: | Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas |
Authors: | Gruppetta, Mark Formosa, Robert Falzon, Sharon Ariff Scicluna, Sabrina Falzon, Edward Degeatano, James Vassallo, Josanne |
Keywords: | Pituitary gland -- Tumors Somatostatin Carcinogenesis Regeneration (Biology) |
Issue Date: | 2017 |
Publisher: | Springer Nature Switzerland AG |
Citation: | Gruppetta, M., Formosa, R., Falzon, S., Ariff Scicluna, S., Falzon, E., Degeatano, J., & Vassallo, J. (2017). Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas. Pituitary, 20(3), 358-371. |
Abstract: | PURPOSE: The pathogenesis of pituitary adenomas (PA) is complex. Ki-67, pituitary tumour transforming gene (PTTG), vascular endothelial growth factor (VEGF), cyclin D1, c-MYC and pituitary adenylate cyclase-activating peptide (PACAP) protein expression were analysed and correlated with tumour and patient characteristics. METHODS: 74 pituitary tumour samples (48 non-functional PA, 26 functional PAs); Immunohistochemical analysis of protein expression, retrospective analysis of MR images and in vitro analysis of octreotide treatment was carried out on GH3 cells. RESULTS: PTTG expression was negatively associated with age and positively with PA size, regrowth and Ki-67 index. Cyclin D1 correlated with Ki-67 and tumour size. c-MYC negatively correlated with size of tumour and age; and correlated with PTTG expression. Somatostatin analogue treatment was associated with lower Ki-67, PTTG and Cyclin D1 expression while T2 hypointense PAs were associated with lower PTTG, cyclin D1, c-MYC and Ki-67. In vitro analyses confirmed the effect of somatostatin analogue treatment on Pttg and Cyclin D1 expression. CONCLUSIONS: Interesting and novel observations on the differences in expression of tumour markers studied are reported. Correlation between Ki-67 expression, PTTG nuclear expression and recurrence/regrowth of PAs, emphasizes the role that Ki-67 and PTTG expression have as markers of increased proliferation. c-MYC and PTTG nuclear expression levels were correlated providing evidence that PTTG induces c-MYC expression in PAs and we propose that c-MYC might principally have a role in early pituitary tumorigenesis. Evidence is shown that the anti-proliferative effect of somatostatin analogue treatment in vivo occurs through regulation of the cell cycle. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/86440 |
Appears in Collections: | Scholarly Works - FacM&SMed |
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ExpressioOfCellCycle.pdf Restricted Access | 1.62 MB | Adobe PDF | View/Open Request a copy |
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