Thyroid-stimulating hormone promotes growth of thyroid carcinomas in transgenic mice with targeted expression of the ret/PTC1 oncogene.
Thyroid carcinomas from mice bearing a thyroid-targeted ret/PTC1 oncogene were studied for responsiveness to endogenous thyroid-stimulating hormone (TSH) to evaluate the effect of TSH on tumor progression. Mice of both sexes were maintained for either 3 or 6 months on a low-iodine diet (LID; < 0.05 ppm) to decrease thyroid hormone production and increase endogenous pituitary TSH secretion. Nontransgenic littermates served as controls. Lesions in mice on LID were observed only in the thyroid and pituitary glands. LID induced marked hyperplasia of thyroid follicular cells of nontransgenic control mice at both time points despite a return of TSH levels to normal values after 6 months of treatment. All transgenic mice had bilateral thyroid carcinomas with histologic features resembling human papillary thyroid carcinoma. The LID resulted in a progressive increase in thyroid area weight and tumor cellularity with the development of a prominent spindle-cell component in the thyroid carcinomas after 6 months. There was no evidence, however, of local or distant metastasis of the thyroid carcinomas. Despite the lack of histologic differentiation, the spindle-cell population retained focal immunoreactivity for thyroglobulin. Our results show that ret/PTC1-induced thyroid follicular cell carcinomas retain TSH responsiveness and maintain a benign biologic behavior despite histologic evidence of anaplasia.
Sagartz
J E
JE
Department of Veterinary Biosciences, Ohio State University, Columbus 43210, USA.
Jhiang
S M
SM
Tong
Q
Q
Capen
C C
CC
D000818:Animals; D002417:Cattle; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007455:Iodine / Q000172:deficiency; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009857:Oncogenes; D010902:Pituitary Gland / Q000166:cytology / Q000473:pathology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012727:Sex Characteristics; D013954:Thyroglobulin / Q000096:biosynthesis* / Q000235:genetics; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000503:physiopathology; D013972:Thyrotropin / Q000097:blood / Q000502:physiology*; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014284:Triiodothyronine; D013972:Thyrotropin; D013954:Thyroglobulin; D007455:Iodine; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; D013974:Thyroxine