Gain-of-function mutations in the TSH receptor and the Galpha(S) subunit occur frequently in hyperfunctioning thyroid nodules and differentiated thyroid carcinomas, whereby the T allele of a common polymorphism (825C>T, rs5443) in the G protein beta3 subunit gene (GNB3) is associated with increased G protein-mediated signal transduction and a complex phenotype.
Mutations L677V and T620I identified in hot thyroid carcinomas were previously characterized in CHO and in 3T3-Vill cell lines, respectively, stably expressing the mutant without determination of TSHR expression.
As disturbed thyrotropin receptor signaling plays a central role in hot thyroid nodules, the identification of effective low-molecular-weight thyrotropin receptor ligands, such as thyrotropin receptor agonists, inverse agonists and antagonists has a pharmacologic potential in the diagnosis and treatment of thyroid cancer, Graves' disease and hot thyroid nodules, respectively.
The mRNA expression levels of CSC- (CD133 and CD44) and ES-related genes (Oct4 and Nanog) were higher in TC tissue than in normal thyroid tissue, whereas the mRNA expression levels of thyroid-specific genes (Tg, TSHR, and TTF1) were higher in normal thyroid tissue than in TC tissue.
All of the transcripts obtained from thyroid carcinomas (both primary and metastatic) were of the same size as the transcripts from normal or benign thyroid tissues, with the exception of 2 cases of differentiated thyroid cancer, in which TSH-R mRNA of lower mol wt (approximately 4.0 kilobases) was found in the absence of alteration in cDNA size and restriction map.
In addition, there was no correlation between NIS and TSHR in thyroid cancer, which may explain why, even after TSH stimulation, 10-20% of these malignant tumors are unable to concentrate enough radioiodine for effective therapy.
The aim of the present study was to investigate the presence TSHR gene mutations in a series of thyroid specimens obtained from 22 consecutive patients with differentiated thyroid carcinomas (8 follicular and 14 papillary).
Methylation of thyroid-specific genes, such as those for sodium/iodide symporter and thyroid-stimulating hormone receptor, is also common in thyroid cancer.
We have established that thyroid hormone receptor beta1 (TRbeta1) is associated with the loss of TSHR gene expression in an anaplastic human thyroid cancer cell line, ARO.
In order to further evaluate the role of TSH in the proliferation and the differentiation of human thyroid carcinoma cells, we have analyzed the function of the TSH receptor in the established thyroid carcinoma cell lines NPA and WRO.
This review examines the evidence for TSHR signaling as an oncogenic pathway and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases.
Qualitative analysis of baseline and stimulated TG, NIS and PDS mRNA showed high sensitivity but low specificity in the prediction of thyroid cancer recurrence or metastases (accuracy under THST = 51%, 43% and 54%, respectively), whereas TPO and TSHR mRNA assays had higher specificity but low sensitivity, with accuracy under THST of 67% and 61%, respectively, that improved when these tests were combined.
TSH receptor mRNA reverse transcription-polymerase chain reaction, the Veracyte and Asuragen commercial methods, and the noncommercial use of BRAF, RAS, RET/PTC, and PAX8/PPARγ testing have promising roles in the diagnosis and treatment of patients with nodular thyroid disease and thyroid cancer.
Lastly, future investigation of epigenetic events occurring at the TSHR and other loci may give better clues for molecular based therapy of undifferentiated thyroid carcinomas.
In this paper we report the results of a screen for structural defects in exon 10 of the TSH-R (which includes the whole serpentine structure, but not the extracellular domain) and of Gs alpha in 30 thyroid carcinomas.
Overexpression of thyroid hormone receptor beta1 is associated with thyrotropin receptor gene expression and proliferation in a human thyroid carcinoma cell line.
Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.