These data suggest a role for the overexpression of c-MET oncogene in the pathogenesis and progression of thyroid tumors derived from the follicular epithelium.
Mutations that lead to constitutive activation of Gs alpha, the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase activity, have been identified in a subset of human growth hormone-secreting pituitary tumors and human thyroid tumors.
Furthermore, these results strongly suggest that the mutated p53 gene plays a crucial role in de-differentiation during the progression of thyroid tumors.
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.
The thyrotropin receptor (TSH-R) is not an oncogene for thyroid tumors: structural studies of the TSH-R and the alpha-subunit of Gs in human thyroid neoplasms.
The presence of p53 mutations almost exclusively in poorly differentiated thyroid tumors and thyroid cancer cell lines suggests that inactivation of p53 may confer these neoplasms with aggressive properties, and further loss of differentiated function.
These results indicate that mutations of the p53 gene are associated with the most aggressive histologic types of thyroid tumors, such as the undifferentiated carcinoma and, to a certain extent, the poorly differentiated carcinoma, and that the alterations of this gene represent a late genetic event in human thyroid carcinogenesis.
Our data suggest that p53 mutations are involved in thyroid carcinogenesis and may play an important role in the malignant transformation of thyroid cells as well as thyroid tumor progression.
We examined the DNA of benign and malignant human thyroid tumors for changes in the methylation state of the genes for human GH, platelet-derived growth factor B-chain, and H-ras.
We have, therefore, analyzed the regulation of HLA-DR-alpha-specific mRNA transcripts, as a model for HLA class II antigen induction, in three established human thyroid cancer cell lines (papillary thyroid cell line NPA, and follicular thyroid cell lines RO-82-W1 and MRO-87-1).
The main conclusions of our study are that 1) the TSH-R gene is expressed in some MTC, which supports, at molecular level, the hypothesis of the existence of mixed follicular-medullary thyroid tumors; and 2) the expression of TSH-R, Tg, and TPO in undifferentiated thyroid cancer is lost.