Development of mammary and cutaneous gland tumors in transgenic mice carrying the RET/PTC1 oncogene.
RET/PTC1 is a chimeric oncogene created by the fusion of the tyrosine kinase domain of RET to the 5'-terminal region of another gene named H4. So far, this oncogene has been found activated only in human papillary thyroid carcinomas. In order to investigate its transforming properties in vivo, we have produced transgenic mice carrying RET/PTC1 under the control of the H4 promoter. The transgene was expressed in several tissues, consistently with the ubiquitous expression of the wild type H4 gene. Mammary adenocarcinomas and, less frequently, hyperplasia of sebaceous glands and rare benign skin tumors, named pilomatrixomas, developed in these mice. The tumors were shown to express the transgene both at the RNA and protein level. These results demonstrate that the transforming ability of the RET/PTC1 oncogene is not restricted to the thyroid epithelium in vivo. Despite its ubiquitous expression, however, RET/PTC1 was able to induce only a limited number of tumor types; specifically mammary epithelium was affected by transgene expression, thus suggesting that RET/PTC1 is able to couple with transforming pathways specific for these glandular cells.
Portella
G
G
Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Universitàdegli Studi di Napoli, Naples, Italy.
Salvatore
D
D
Botti
G
G
Cerrato
A
A
Zhang
L
L
Mineo
A
A
Chiappetta
G
G
Santelli
G
G
Pozzi
L
L
Vecchio
G
G
Fusco
A
A
Santoro
M
M
D000367:Age Factors; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D005260:Female; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012627:Sebaceous Glands / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology; D014018:Tissue Distribution
C088832:CCDC6 protein, human; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; C093573:ret-PTC fusion oncoproteins, human