Endocrine Abstracts

Pituitary adenomas are frequent intracranial tumors that often associate with the hypersecretion of pituitary hormones or may be non-secreting (nonfunctioning pituitary adenomas, NFPA). Tumors resembling human NFPAs develop with complete penetrance in rats affected by the multiple endocrine neoplasia syndrome, MENX. This syndrome is caused by a germline loss of function mutation in p27^Kip1. Gene expression array analysis performed in our group identified a considerable number of genes deregulated in rat pituitary tumors compared to normal pituitary tissues. Some of the deregulated transcripts are associated with angiogenesis, including vascular endothelial growth factor (Vegf), angiopoietin-1 (Ang-1) and -2 (Ang-2). VEGF and ANG-2 were found to promote angiogenesis in several tumor types, while ANG-1 inhibits this process and stabilizes mature vessels. We analyzed mRNA and protein expression changes of these 3 genes in the pituitary adenomas of MENX-affected rats and compared the results with similar analyses conducted on the corresponding human tumors. We could show that Ang-1 was down regulated in rat and human NFPAs whereas Ang-2 mRNA was highly expressed in almost all of the rat pituitary adenomas and was enhanced in less than the half of the human NFPAs. Vegf mRNA was up-regulated in MENX-rats but not in NFPAs. At the protein level, we have so far set up the immunohistochemical staining for Ang1 and -2 on both rat and human tumors. We could show that rat pituitary adenomas and human NFPAs show reduced cytoplasmic Ang-1 staining compared to adjacent non tumor cells while Ang-2 was more strongly expressed in tumor areas.