Endocrine Abstracts

Epigenetic deregulation is emerging as a component of the parathyroid tumorigenesis. We identified a long non-coding RNA (LNCRNA) signature clearly distinguishing parathyroid adenomas (PAds) and carcinomas from normal glands. Among the deregulated LncRNAS, HAR1B was upregulated in PAds harboring the common chromosome 11q loss of heterozygosity (Chr11q-LOH; n=10) compared with PAds harboring normal chromosome 11 haplotype (Chr11q-WT; n=12; P&...

We previously described aberrant expression of microRNAs belonging to the chromosome 19 cluster (C19MC) and the close miR-371-373 cluster in two-thirds of parathyroid carcinomas (PCas). Therefore, we investigated the involvement of the miR-371-373 cluster in parathyroid tumours, where miR-372 was the most consistently upregulated. miR-372 is known to be highly expressed in human embryonic stem cells and definitely downregulated upon differentiation. Moreover, miR-372 promotes ...

Though there is no evidence of a constitutive nuclear accumulation of β-catenin, the Wnt/β-catenin pathway might be deregulated in parathyroid tumours. We investigated unphosphorylated active β-catenin distribution by western blot in 16 typical parathyroid adenomas (PAds): β-catenin accumulation in the nuclear protein fractions varied from the levels detected in Caco-2 cells with constitutively active Wnt signalling (three PAds) to the levels measured in HE...

Parathyroid carcinomas (PCas) are rare endocrine malignant neoplasia characterized by an abnormal PTH secretion and, consequently, severe and uncontrolled hypercalcemia. Clinically, the preoperative diagnosis can be misleading, because PCas share some molecular and clinical similarities with benign lesions and are often indolent. The histological diagnosis of carcinoma is achieved based on the presence of mitotic nuclear figures, capsular invasion, parenchyma infiltration, vas...

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Embryonic transcription factors have been involved in tumourigenesis. The transcription factor TBX1 regulates the embryonic parathyroid cells fate. Indeed, it has never been investigated in human adult parathyroids. Here, expression, function and regulation of the TBX1 gene were analyzed in adult normal and tumour parathyroid tissues. Immunohistochemistry identified 30–70% (mean±S.E.M, 52.0±7.3%) of cells expressing TBX1 at nuclear levels...

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 w...

Patients with primary hyperparathyroidism (PHPT) are at risk of chronic kidney disease (CKD). PHPT patients (n=190, 146 females and 44 males, aged 59.7±14.2 years) and non-hypertensive, non-diabetic age- and sex-matched healthy controls were evaluated for serum cystatin C and creatinine. PHPT patients and controls with established CKD were excluded. Serum cystatin C was measured by immunonephelometric assay and calculation of estimated glomerular filtration rate ...

Parathyroid glands regulate bone metabolism through PTH, while bone modulates parathyroid function through calcium and FGF23. Bone releases the matrix protein osteocalcin (OC), whose hormone function is increasingly evident. We tested the hypothesis that OC may modulate parathyroid function. The 6 hours-stimulation of human parathyroid cells derived from adenomas (PAds) (n = 5) with γ-carboxylated OC (GlaOC; 40–60 ng/ml) increased the expression levels ...

Cancer cells and embryonic stem cells share many key biological properties and have common genetic signature: transcription factors regulating self-renewal and differentiation have been found expressed in human cancer cells. We focused our attention on TBX1, the gene involved in 22q11.2 microdeletion/DiGeorge syndrome, which is involved in heart, thymic and parathyroid cells differentiation.Real-time PCR, western blot and immunohistochemistry de...