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Title: | Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas |
Authors: | Formosa, Robert Borg, Joseph J. Vassallo, Josanne |
Keywords: | Pituitary gland -- Diseases Adenoma DNA microarrays Intracranial tumors |
Issue Date: | 2017-08 |
Publisher: | Bioscientifica |
Citation: | Formosa, R., Borg, J., & Vassallo, J. (2017). Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas. Endocrine-Related Cancer, 24(8), 445-457. |
Abstract: | Pituitary adenomas (PA) represent the largest group of intracranial neoplasms and yet the molecular mechanisms driving this disease remain largely unknown. The aim of this study was to use a high-throughput screening method to identify molecular pathways that may be playing a significant and consistent role in PA. RNA profiling using microarrays on eight local PAs identified the aryl hydrocarbon receptor (AHR) signalling pathway as a key canonical pathway downregulated in all PA types. This was confirmed by real-time PCR in 31 tumours. The AHR has been shown to regulate cell cycle progression in various cell types; however, its role in pituitary tissue has never been investigated. In order to validate the role of AHR in PA behaviour, further functional studies were undertaken. Over-expression of AHR in GH3 cells revealed a tumour suppressor potential independent of exogenous ligand activation by benzo α-pyrene (BαP). Cell cycle analysis and quantitative PCR of cell cycle regulator genes revealed that both unstimulated and BαP-stimulated AHR reduced E2F-driven transcription and altered expression of cell cycle regulator genes, thus increasing the percentage of cells in G0/G1 phase and slowing the proliferation rate of GH3 cells. Co-immunoprecipitation confirmed the interaction between AHR and retinoblastoma (Rb1) protein supporting this as a functional mechanism for the observed reduction. Endogenous Ahr reduction using silencing RNA confirmed the tumour suppressive function of the Ahr. These data support a mechanistic pathway for the putative tumour suppressive role of AHR specifically in PA, possibly through its role as a cell cycle co-regulator, even in the absence of exogenous ligands. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/86438 |
Appears in Collections: | Scholarly Works - FacHScABS Scholarly Works - FacM&SMed |
Files in This Item:
File | Description | Size | Format | |
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Endocrine-Related Cancer] Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas.pdf | 2.24 MB | Adobe PDF | View/Open |
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