ECE2011 Poster Presentations Endocrine tumours and neoplasia (37 abstracts)
1Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, IRCCS Policlinico San Donato, San Donato M.se (MI), Italy; 2Molecular Biology Laboratory, IRCCS Policlinico San Donato, San Donato M.se (MI), Italy; 3Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Milan, AO San Paolo, Milan, Italy; 4Stem Cell Laboratory, Department of Neurological Sciences, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milan, Italy; 5Endocrinology Unit, IRCCS Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 6Endocrine Surgery, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 7Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy; 8Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 9Endocrine Unit, Department of Medical Sciences, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
The embryonic transcription factor TBX1 plays a critical role in cell differentiation during organogenesis of the parathyroid glands. Here we demonstrated that TBX1 mRNA and protein were detected in human adult normal parathyroid tissues (n=3). Immunostaining showed that TBX1 protein was expressed in endothelial CD31+, alfa-SMA+ cells. By contrast, TBX1 mRNA and protein was expressed at higher levels in parathyroid typical adenomas (n=23), where TBX1 staining was positive in parathyroid PTH+ cells with a cytoplasmic and nuclear localization. Functional studies were performed in HEK293 cells as they expressed TBX1. The activation of the calcium sensing receptor (CaSR) by stimulating for 24-h HEK293 cells stably transfected with the human CaSR with 15 mM calcium as well as with 10100 nM R-568, the CaSR agonist cinacalcet, induced a significant reduction in TBX1 mRNA levels. Thus, CaSR downregulation in parathyroid tumours might be related with the TBX1 overexpression. Overexpression of TBX1 mRNA and protein were observed also in parafibromin-expressing parathyroid cancers (n=3). TBX1 mRNA and protein were downregulated in parafibromin negative parathyroid carcinomas (n=14), suggesting that Wnt/β-catenin activation might inhibit TBX1 expression. In HEK293 cells TBX1 mRNA were inhibited by β-catenin accumulation induced by 24-h treatment with 120 nM lithium chloride, while β-catenin degradation induced by 40-min pretreatment with 10100 nM calyculin A determined an increase in TBX1 mRNA levels. Further functional studies on the effect of silencing and transfection of TBX1 are ongoing. In conclusion, the present data demonstrated that: i) TBX1 is expressed in adult parathyroid tissues; ii) TBX1 impaired expression contributes to parathyroid tumorigenesis; iii) TBX1 is a new target of the CaSR and Wnt/β-catenin pathways. TBX1 provides a potential therapeutic target for parathyroid tumors.