Fig. 7. Pituitary adenomas from pituitary-specific Aip-knockout mice or from human patients have overexpression of the RET/GDNF survival pathway.
A Pituitary extracts from15-month old AipFlox/Flox;Hesx1Cre/+ knockout mice compared to AipFlox/Flox;Hesx1+/+ control male mice. B Increased levels of GDNF, phospho-AKT and phospho-mTOR and reduced expression of phospho-p53 and AIP are found in mutant animals. C Expression of the CDKN2A probe set, including three probes, in AIP-FIPA pituitary adenomas compared to sporadic pituitary adenomas, retrieved from ReGEO GSE63357, a study using the Affymetrix HG-U133 Plus 2.0 array. Only 209644_x_at includes oligos specific for the CDKN2A-ARF specific Exon 1, while the other probes contain oligos specific for the other protein isoform CDKN2A-p16 specific Exon 1 (21156_at), or the common Exon 3 (207039_at). D Immunohistochemistry comparing somatotroph macroadenomas from sporadic (Sp GH) or AIP-FIPA tumours (AIP+). E Representative stainings for RET (total RET HPA008356), GDNF and GFRα1. Sections were counterstained with haematoxylin. F Corresponding fields within the same sample, showing heterogeneity of GDNF staining compared to GH. (N = 3; Mann–Whitney, *p < 0.05; numbers, when p is non-significant but approximates to significant levels).