Endocrine Abstracts

Background: Heterozygote mutations in 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: Functional assays (invasion, MTS and colony formation) were carried out after silencing of AIP in BxPC3 using siRNA targeting human AIP. Invasion assays were performed using BioCoat-Matrigel Invasion Chambers. MTS assays were used to measure the metabolic activity at 24, 48, 72, 96 and 120 h after transfection. Colony formation assays were also performed to detect changes in proliferation rates of these cells.

Results: Silencing endogenous AIP in BxPC3 cells significantly increased the number of invading cells compared to non-targeting siRNA controls (P<0.04). MTS assays showed AIP silencing caused an increase in metabolic activity compared to non-targeting siRNA controls at 72, 96 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: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.