Thyroid Proteins and Hormone Synthesis in Human Thyroid Cancer

Abstract

Thyroid iodoproteins and hormone synthesis have been studied in vivo and in organ culture in 44 cases of thyroid cancer. In a few cases, Tg1) (17–19 S) is virtually absent; a portion of the light fractions (3–8 S), which seems to represent some precursors of Tg, incorporated in culture the 14C-amino acids. In most of the cases, the solubility profiles, sedimentation patterns as well as electrophoretic migration of proteins were normal. The content of Tg and the concentration of stable iodine (127I) in Tg are less than that of "normal" tissues, and the deficiency in iodination appears to be more pronounced than the depression of the Tg synthesis. Most frequently the radioiodine uptake is very low and most of the iodine remains in the gland as iodide and MIT. In those tissues which organify radioiodine, it is incorporated into tyrosine molecules and is metabolized to the stage of iodothyronines (T4 + T3); there must then be little or no defect in coupling reactions. There is a linear relation between the concentration of stable iodine in Tg and the level of hormone synthesis, as we have found in "normal" gland and benign thyroid diseases. These results suggest that the overall disorder seen in thyroid cancer tissues appears to involve one of the initial steps of hormone synthesis. The very low mean iodination of Tg in these tissues suggests a great heterogeneity in the functional activity throughout the tumour. TSH has a very variable effect on thyroid cancer tissues maintained in organ culture: in 46 % of the cases the hormone has no effect. In some instances TSH may significantly increase the incorporation of radioiodine into soluble iodoproteins, Tg as well as the albumin fraction.

Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line

“…Our assay, therefore, likely underestimates cytotoxicity caused by 131 I. Most differentiated thyroid cancers have varying degrees of impaired iodide organification (53)(54)(55), but 131 I therapy is still effective in most thyroid cancer, even when organification is diminished or absent.…”

Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism

“…Although papillary and follicular thyroid carcinomas retain the majority of biological properties of normal thyroid cells, a variety of biochemical defects has been demonstrated (28)(29)(30). Indeed, impaired intrathyroidal iodine metabolism represents one of the most peculiar abnormalities present in thyroid neoplastic tissue.…”

Expression of the Na+/I−Symporter Gene in Human Thyroid Tumors: A Comparison Study with Other Thyroid-Specific Genes1

“…However, its concentration was lower than that in normal tissue and was lowest in poorly differentiated histotypes (8,13,14). In thyroid cancer tissue, Tg was poorly iodinated, and hormonal production of T 3 and T 4 was rarely observed (11,12,21). The present study suggests that its poor degree of iodination may be related to defects in both the iodine-trapping ability and the iodination process.…”

“…In in vitro studies, multiple biochemical abnormalities have been found, including a low intrathyroid concentration of iodine, a low degree of iodination of Tg, and a low rate of thyroid hormone synthesis (11,12). The biological activity of peroxidase, a key thyroid enzyme in the iodide organification process, although normal in benign cold adenomas, was decreased in thyroid carcinomas (10,15), whereas TSH-R were detected in most differentiated thyroid tumors, including thyroid carcinomas (8,14,19).…”