Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 P217

SFEBES2009 Poster Presentations Endocrine tumours and neoplasia (39 abstracts)

Is the anti-proliferative effect of AIP (aryl hydrocarbon receptor interacting protein) via ZAC transcription factor?

Neda Alband , Susanna Igreja , Harvinder S Chahal , Ashley B Grossman & Marta Korbonits

William Harvey Research Institute, London, UK.

Background: Pituitary adenomas are relatively common in the general population, but the pathogenesis of these tumours remains largely unknown. Recently, germline mutations have been described in the AIP (aryl hydrocarbon receptor interacting protein) gene in several patients with familial isolated pituitary adenomas (FIPA). This gene is located on chromosome 11q13 and loss of heterozygosity at this locus as well as functional data from our group demonstrates a tumour suppressor role for AIP1. The mechanism by which AIP exerts its tumour suppressive action in the pituitary remains unclear. A recent study has demonstrated that up-regulation of the AIP gene in the liver of transgenic mice increases the expression of ZAC/PLAGL1, a tumour suppressor gene2. We hypothesised that AIP mediates its tumour suppressor role in the pituitary via up-regulation of ZAC.

Aims and objectives: To study the effect of wild-type and mutant AIP on ZAC mRNA expression in GH3 cells (rodent somato-mammotroph pituitary cell line).

Methods: GH3 cells were transiently transfected with wild-type and mutant AIP (C238Y and R304X) as well as empty vector plasmids. The expression of ZAC mRNA was assessed by real-time PCR.

Results: Over-expression of wild-type AIP significantly increased ZAC mRNA expression compared to the empty vector and the mutant AIP (C238Y and R304X).

Conclusion: ZAC mRNA expression was significantly increased in GH3 cells transiently transfected with wild-type AIP compared to the empty vector and mutant AIP. Our results suggest AIP may exert its tumour suppressor role in the pituitary by up-regulating ZAC mRNA expression.

References: 1. Leontiou CA et al. Journal of Clinical Endocrinology and Metabolism 2008 93 2390–2401.

2. Hollingshead BD et al. Molecular Pharmacology 2006 70 2096–2107.

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