Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
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Query: UMLS:C0221002 (
primary hyperparathyroidism
)
4,921
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Primary hyperparathyroidism
(pHPT) is rarely caused by parathyroid carcinoma (PC, <1-5% of pHPT cases). The TET proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and inactivation by mutation or epigenetic deregulation of
TET1
and
TET2
play important roles in various cancers. Recently, we found that 5hmC was severely reduced in all of the analyzed PCs and with deranged expression of TET1 for the majority of PCs. Here, we have examined the expression of the TET2 protein in 15 5hmC-negative PCs from patients who had local invasion or metastases. Cell growth and cell migratory roles for
TET2
as well as epigenetic deregulated expression were addressed. Immunohistochemistry revealed very low/undetectable expression of
TET2
in all PCs and verified for two PCs that were available for western blotting analysis. Knockdown of
TET2
in the parathyroid cell line sHPT-1 resulted in increased cell growth and increased cell migration. DNA sequencing of
TET2
in PCs revealed two common variants and no obvious inactivating mutations. Quantitative bisulfite pyrosequencing analysis of the
TET2
promoter CpG island revealed higher CpG methylation level in the PCs compared to that in normal tissues and treatment of a PC primary cell culture with the DNA methylation inhibitor 5-aza-2'-deoxycytidine caused increased expression of the methylated
TET2
gene. Hence, the data suggest that deregulated expression of
TET2
by DNA hypermethylation may contribute to the aberrantly low level of 5hmC in PCs and further that
TET2
plays a cell growth and cell migratory regulatory role and may constitute a parathyroid tumor suppressor gene.
...
PMID:A role for
TET2
in parathyroid carcinoma. 2864 44
