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.
The present study indicates the normal patterns of DNA and RNA hybridization in a variety of thyroid tissues and disease states, and demonstrates that pathologic thyroid samples, with the possible exception of thyroid cancer, were not associated with specific nucleotide abnormalities in the unique area of the TSH receptor that was studied.
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 the present study we compared the TSH receptor and c-myc mRNA levels in different stages of thyroid carcinomas to identify whether they are useful markers for thyroid tumour biological behaviour and prognosis.
We, therefore, isolated neomycin-resistant stable human thyroid carcinoma cell (WRO cell) transfectants overexpressing intact human TSH receptor to evaluate the functional role of TSH receptor on carcinoma cells.
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.
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).
Overexpression of thyroid hormone receptor beta1 is associated with thyrotropin receptor gene expression and proliferation in a human thyroid carcinoma cell line.
It is proposed that the constitutively activated TSHR genes detected in the thyroid carcinomas, may have played an oncogenic role, participating in their development through these two pathways.
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.
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.
Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer.
Methylation of thyroid-specific genes, such as those for sodium/iodide symporter and thyroid-stimulating hormone receptor, is also common in thyroid cancer.
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.
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.
Among these, thyroglobulin, and more recently thyroid-stimulating hormone receptor mRNAs' provide high diagnostic sensitivity and specificity for thyroid cancer detection.
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.
As such, this article addresses the following aspects of intragenic mutations in thyroid cancer: thyroid stimulating hormone receptor and guanine-nucleotide-binding proteins of the stimulatory family mutations in hyperfunctioning tumors; mutations in RAS and other genes and aneuploidy; PAX8-PPARgamma rearrangements; BRAF mutations; mutations in oxidative phosphorylation and Krebs cycle genes in Hürthle cell tumors; mutations in succinate dehydrogenase genes in medullary carcinoma and C-cell hyperplasia; and mutations in TP53 and other genes in poorly differentiated and anaplastic carcinomas.