Endocrine Abstracts (2012) 28 OC5.7

The role of the familial pituitary adenoma gene, AIP, in the proliferative and invasive activity of a malignant pancreatic cell line

Jumana Saleh, Sayka Barry & Marta Korbonits

Endocrinology, William Harvey Research Institute, London, United Kingdom.

Background: Heterozygote mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose carriers to young-onset pituitary adenomas, most often somatotroph or lactotroph adenomas. No other tumour type has been consistently detected in AIP mutation positive families, despite the fact that AIP is ubiquitously expressed. Current clinical and experimental data suggest that AIP is a tumour suppressor gene.

Aims: To investigate the tumour suppressor role of AIP in a non-pituitary malignant cell line by exploring whether silencing of AIP would affect the invasive and proliferative properties of a highly invasive human pancreatic cancer cell line BxPC3.

Methods: Migration, invasion, MTS and colony formation assays were carried out after silencing of AIP in BxPC3 using siRNA targeting human AIP. Results Silencing endogenous AIP in BxPC3 cells significantly increased the number of invading cells compared to non-targeting siRNA controls (P<0.04). However, silencing AIP did not affect the migration of BxPC3 cells. MTS assays showed AIP silencing caused an increase in metabolic activity compared to non-targeting siRNA controls at 72 h, 96 h and 120 h (P<0.01 for all). Furthermore, knockdown of AIP led to an increase in the number of colonies compared to siRNA controls (P<0.01).

Conclusion: These results indicate that lack of AIP increased the proliferative and invasive behaviour of this non-pituitary malignant cell line, suggesting an inhibitory role in cell invasion and proliferation and supporting the function of AIP as a tumour suppressor. These data suggest that the tumour suppressor effect of AIP is not limited to pituitary cells and can counteract aggressive behaviour of a cancer cell line. This raises questions as to why AIP mutations are solely associated with pituitary adenomas and no other tumour types.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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