Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice.
Gene rearrangements activating the RET proto-oncogene are frequently associated with human thyroid carcinomas belonging to the papillary subtype. These arrangements cause the fusion of the tyrosine-kinase domain of RET to the 5'-terminal region of different genes creating the RET/PTC chimeric oncogenes. Here we report the generation of transgenic mice lines expressing the RET/PTC1 oncogene under the control of the thyroid-specific rat thyroglobulin promoter. RET/PTC1-transgenic mice developed thyroid tumors displaying the histological aspect of papillary carcinomas. These tumors were slowly progressive and did not cause premature death of the animals. Two additional mice developed areas of thyroid hyperplasia. Immunohistochemical and reverse-transcriptase polymerase chain reaction analyses confirmed the thyroid-specific expression of the transgene. Given the frequency of activating rearrangements of RET in human papillary thyroid carcinomas we conclude that this animal system could be a good model for studying the neoplastic progression of thyroid carcinomas.
Santoro
M
M
Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Napoli- Italy.
Chiappetta
G
G
Cerrato
A
A
Salvatore
D
D
Zhang
L
L
Manzo
G
G
Picone
A
A
Portella
G
G
Santelli
G
G
Vecchio
G
G
Fusco
A
A
D000818:Animals; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D029721:Drosophila Proteins; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013954:Thyroglobulin / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D013954:Thyroglobulin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; C495001:Ret protein, rat; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C