propylthiouracil and Carcinoma--Papillary

RET/PTC1 is a rearranged form of the RET proto-oncogene detected in human papillary thyroid carcinomas. We previously showed that thyroid-targeted expression of RET/PTC1 leads to thyroid tumor formation in Tg-PTC1 transgenic mice. Signal transduction pathways mediated by phosphotyrosine 294, 404, or 451 in RET/PTC1 have been shown to be critical for RET-induced transforming activity in vitro. To investigate the contribution of these signaling pathways in RET/PTC1-induced thyroid tumor formation in vivo, we generated and characterized transgenic mice expressing thyroid-targeted RET/PTC1 mutants carrying a site-directed mutation changing tyrosine (Y) to phenylalanine (F) at the residue 294, 404, or 451. In contrast to the 100% tumor formation rate in Tg-PTC1 transgenic mice, tumor formation rates were significantly decreased in Tg-PTC1-Y294F (6%), Tg-PTC1-Y404F (41%), and Tg-PTC1-Y451F (30%) transgenic mice. This indicates that signaling pathways mediated by pY294, pY404, and pY451 do play a role in RET/PTC1-induced tumor formation. However, as tumors are still able to form in some mice within these three mutant transgenic groups, it indicates that none of the signaling pathways mediated by pY294, pY404, or pY451, are solely essential for RET/PTC1-induced tumor formation.

Topics: Amino Acid Substitution; Animals; Antithyroid Agents; Carcinoma, Papillary; Cell Transformation, Neoplastic; Diet; Humans; Iodine; MAP Kinase Signaling System; Mice; Mice, Transgenic; Mutagenesis, Site-Directed; Oncogene Proteins; Oncogene Proteins, Fusion; Phosphorylation; Phosphotyrosine; Propylthiouracil; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Signal Transduction; Thyroid Neoplasms; Tubulin

Traditionally, Basedow-Graves disease was considered a protection against thyroid cancer. However, recent reports suggest that cancer occurs with a higher frequency than expected and is more aggressive in this disease. We report six patients with hyperthyroidism due to a Basedow Graves disease that presented a palpable thyroid nodule, which was cold in the scintiscan and solid in the ultrasound examination. Fine needle cytology disclosed cancer in five cases (two with cytological features of greater aggressiveness) and a nodular hyperplasia in one. The diagnosis was confirmed in the surgical piece in all patients. We conclude that Basedow-Graves disease and thyroid cancer, which can have an increased aggressiveness, may coexist.

Topics: Adolescent; Adult; Carcinoma, Papillary; Female; Graves Disease; Humans; Male; Middle Aged; Propranolol; Propylthiouracil; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography

Effects of hormones (E2: estradiol, TP: testosterone) and propylthiouracil (PTU) on the growth of transplantable rat thyroid tumor (F2D1) having estrogen receptors were studied. Rat thyroid neoplasms, induced by N-bis (2-hydroxypropyl) nitrosamine, were inoculated subcutaneously from donor to recipient rats, in order to establish 16 transplantable rat thyroid tumor lines. The grafts were used for histological studies and for the assay of estrogen receptor (ER) and androgen receptor (AR). Of these lines, we designated papillary carcinoma, which was positive for ER (N: 12.5fmol/mg protein, Kd: 0.4nM) but negative for AR, as F2D1. For studies on the effects of sex hormones and PTU on the growth of transplantable tumors, the rats which had been inoculated with tumors were divided into the following 8 groups; (1) Intact, (2) PTU, (3) ovariectomy (OV), and (4) OV + E2 for female, and (5) Intact, (6) PTU, (7) castration (CA), and (8) CA + TP for male.. The growth rate of F2D1 in female rats was decreased by OV, but no change was observed in OV + E2 as compared with Intact. CA and CA + TP in male rats did not influence the growth rate. PTU produced a significant increase in the growth rate in both sexes. These results demonstrate that estrogen and PTU act on the growth of ER-positive rat thyroid tumors.

Topics: Animals; Carcinoma, Papillary; Estradiol; Female; Male; Neoplasm Transplantation; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Estrogen; Testosterone; Thyroid Neoplasms

Topics: Animals; Carcinoma, Papillary; Iodine Isotopes; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Propylthiouracil; Rats; Thyroid Neoplasms