Defective Thyroglobulin Synthesis in an Experimental Rat Thyroid Tumor: LACK OF MEMBRANE-BOUND SIALYLTRANSFERASE ACTIVITY

Abstract

Abstract The incorporation of carbohydrates has been studied in vitro in the experimental rat thyroid tumor 1-1C2. The uptake of N-[3H]acetylmannosamine, a precursor of sialic acid, is less than 5% of that in normal thyroid gland; no label is found in 19 S thyroglobulin or its precursors either in the soluble or in the solubilized proteins. N-[3H]Acetylglucosamine is incorporated at a slower rate than in normal thyroid gland and is present in the membrane-bound thyroglobulin; there is no conversion into sialic acid in the soluble thyroglobulin of tumor as occurs in normal thyroid. [14C]Mannose and [14C]galactose are incorporated at an almost normal rate and [14C]fucose, at a subnormal rate; they are present mainly in the particle-bound proteins as ∼18 S thyroglobulin and its precursors. Measurement of sialyltransferase activity showed that, with desialylated thyroglobulin as acceptor, the 22,000–105,000 x g pellet of tumor contains ∼3% of normal sialyltransferase activity, and the soluble fraction contains ∼25% of normal activity. Desialylated fetuin and orosomucoid are generally better acceptors than desialylated thyroglobulin for tumor sialyltransferase. The findings indicate that defective thyroglobulin release and absence of incorporation of sialic acid into thyroglobulin coexist in this tumor. The very low activity of thyroglobulin-specific sialyltransferase activity in the tumor particulate fraction accounts for the failure of sialic acid incorporation into thyroglobulin and may explain the defect in thyroglobulin release.