ESEBEC2016 ESE Basic Course on Endocrine and Neuroendocrine Cancer 2016 AIP and the somatostatin signalling in pituitary tumours (2 abstracts)
Germline mutations in the AIP gene predispose to the development of pituitary adenomas, most often GH secreting tumours. These patients often poorly respond to medical therapy with somatostatin analogues.
There are two mechanisms suggested to be involved in this poor response.
One suggests that the somatostatin-induced upregulation of the tumour suppressor gene Zac1 involves AIP. SSTR2 agonist treatment leads to AIP upregulation in vivo and in vitro and AIP overexpression or downregulation leads to increase or drop of ZAC1 levels.
The other mechanism suggests the involvement of the Gαi-2 protein, one of the G proteins known to be activated by SSTRs, as this was found to be downregulated in AIP insufficient cells.
These mechanisms could be operational not just in patients with germline AIP mutation, but also in patients with low AIP expression due to other factors.
It is currently unknown what are the exact molecular mechanisms involved in these effects. Future data on multireceptor ligand pasireotide in patients with AIP mutation or low AIP levels will help to clarify the mechanism.
Further deciphering these molecular pathways will provide a better understanding of the mechanism of action of this class of drugs and will have important therapeutic implications.