Endocrine Abstracts

With the aim of identifying genes involved in the development of pituitary tumors, we used the mRNA differential display technique comparing tumor and normal pituitary cells. Two genes have been identified to be involved in pathogenesis process: in prolactinomas obtained from Dopamine D2R knockout female mice, we have found differential expression of the cytokine BPMP-4 and in clones of the tumoral lactosomatroph cell line GH3 cell line overexpressing the cytokine IL6 signal transducer gp130, which have enhanced tumorigenecity in nude mice, we found the expression of a novel gene RSUME.

BMP-4 has a dual role in lactotrophas and corticotrophs: it is augmented (and its antagonist noggin decreased) during prolactinoma development stimulating this cell proliferation, while, on the contrary, in corticotrophinomas BMP-4 has an inhibitory action. In both cases the action is different of that of TGF β and involves a cross talk of smad-4 with steroid receptors. RSUME expression is induced under hypoxic conditions, increases VEGF and HIF expression, which correlates with increased angiogenic potential of the lactosomatotrophic gp130 clones, and has a potential role during vascularization. Its mechanism of action involves the stabilization of these proteins through sumoylation. RSUME is overexpressed in human pituitary adenomas, particularly in necrotic areas. These proteins provide new interesting targets for inhibiting differente steps involved in the development of pituitary adenomas.

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 are unavailable.