ECE2016 Guided Posters Endocrine Tumours (10 abstracts)
Expression and regulation of the early embryonic stem cell genes in parathyroid tumours
Chiara Verdelli 1 , Irene Forno 2, , Stefano Ferrero 2, , Vito Guarnieri 4 , Alfredo Scillitani 5 , Filomena Cetani 6 , Leonardo Vicentini 7 , Gianni Balza 8 , Edoardo Beretta 9 , Pasquale Creo 10 , Valentina Vaira 2, & Sabrina Corbetta 1
1Endocrinology Unit, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese (MI), Italy; 2Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy; 3Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 4Medical Genetics, IRCCS Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 5Endocrine Unit, IRCCS Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 6Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy; 7Endocrine Surgery, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 8Endocrinology Unit, Ospedale Manzoni, Lecco, Italy; 9Endocrine Surgery, IRCCS Ospedale San Raffaele, Milan, Italy; 10Laboratory of Stem Cell for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese (MI), Italy.
An embryonic gene signature has been suggested in parathyroid tumours. We investigated the expression of early embryonic stem cell (ESC) genes in parathyroid tumours. POU5F1/OCT4, SOX2 and NANOG transcripts were detected in almost all parathyroid adenomas (PAds; n=22) and atypical PAds (n=3), besides the variable expression of ESC genes KLF4, EGR1, and REX1/ZFP42. OCT4, SOX2 and NANOG proteins expression were analyzed by immunohistochemistry in archival series of tumours and normal parathyroid glands. Parathyroid carcinomas (n=8) had more NANOG-expressing cells (mean positive cells 40%) compared to PAds (n=11; mean positive cells 10%), while PAds (n=22) showed a higher proportion of SOX2-expressing cells, though SOX2-expressing cells occurred in half of tumours. PAds-derived cells expressing the pluripotency genes were negative for PTH immunostaining. The ESC pluripotency is regulated by the Wnt/β-catenin and by the bone morphogenetic proteins (BMP) signalling. Active β-catenin highly accumulated at membrane and cytoplasm levels in normal glands (n=4) and in PAds (n=16), though PAds were heterogeneous showing parenchymal zones where cells had very low active β-catenin levels confined at membrane. Despite the absence of robust nuclear accumulation, β-catenin is transcriptionally active in parathyroid neoplasia: treatment of PAds-derived cells (n=6) with 10–20 mM Lithium Chloride increased the Wnt gene targets AXIN2, DKK1, ZEB1, and modulated the expression of POU5F1/OCT4, SOX2 and NANOG mRNA levels depending on the time course of β-catenin activation. Investigating samples from 25 PAds, we observed that PAds expressing AXIN2 (n=6) had abundant NANOG, SOX2 and WNT5A transcripts. Moreover, stimulation of PAds-derived cells for 24 h with 50 and 100 nM BMP4 induced significant increases in ID1/inhibitor of DNA binding 1 (about threefold the basal levels) and Gremlin transcripts suggesting that PAds-derived cells are responsive to BMP signalling. Nonetheless, any effect could be detected on ESC genes transcripts levels by a short term BMP pathway activation. In conclusion, parathyroid tumour cells expressed the ESC genes, whose expression might be modulated by deregulated β-catenin.
Volume 41
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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