Endocrine Abstracts

Introduction: Tumours with aryl hydrocarbon receptor interacting (AIP) mutations often show an unusually aggressive and invasive clinical course as up to 80% of AIP positive pituitary adenomas have a certain degree of extrasellar extension. The exact mechanisms by which AIP inactivation promotes an aggressive behaviour remain unknown. The majority of adenohypophysis is composed of sinuous cords of epithelial cells and consequently, molecules that can induce remodelling changes in the epithelial tissue of the normal pituitary gland are of a particular interest.

Methods: The Drosophila melanogaster AIP orthologue gene CG1847 encodes for a protein with a similar size and structure. To study CG1847, we generated loss of function flies using two independent methods: RNA-interference and gene knockout via P-element imprecise excision. We specifically addressed CG1847 function in the developing Drosophila wing, a tissue consisting of only two epithelial layers. We evaluated the resulting phenotypes in 2 stages of development: at pupal stage and at adulthood.

Results: Silencing or deletion of CG1847 caused wing blisters in adults. Analysis of developing wings at pupal stage revealed a marked deregulation of the actin network in the wing epithelium, which resulted in loss of adhesion between the two cell layers. Furthermore, actin dysregulation resulted in wing vein widening as vein cells failed to form a lumen, enhancing the loss of adhesion phenotype.

Conclusions: In conclusion, the study of CG1847, the Drosophila orthologue of human AIP, revealed an exciting novel role for this protein in cell adhesion. The mechanism of CG1847 involvement in cell adhesion is via actin cytoskeleton deregulation, supported also by the wing vein widening. This novel possible interaction with cytoskeletal proteins suggests a putative involvement of AIP in cell motility and tumour invasiveness as cytoskeletal disorganisation is an important feature of epithelial-mesenchymal transition, a process leading to increased migratory capacity resulting in a more aggressive phenotype.