1. Medullary thyroid carcinomas in transgenic mice expressing a polyoma carboxyl-terminal truncated middle-T and wild type small-T antigens
- Author
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C. Della Rocca, Paolo Amati, Laura Pozzi, Patrizia Rovere, A Felici, Marco Giorgio, M Santoro, I Manni, N Krauzewicz, A., Felici, M., Giorgio, N., Krauzewicz, C. D., Rocca, Santoro, Massimo, P., Rovere, I., Manni, P., Amati, and L., Pozzi
- Subjects
Cancer Research ,viruses ,Antigens, Polyomavirus Transforming ,medicine.disease_cause ,Medullary ,Neoplasms, Multiple Primary ,Mice ,genetics, Organ Specificity, Receptor ,Multiple Primary ,oncogene ,medullary thyroid carcinoma ,Transgenes ,Sequence Deletion ,Thyroid ,genetics/pathology, Transgenes, Vibrissae ,ErbB Receptors ,medicine.anatomical_structure ,Medullary carcinoma ,Animals, Antigen ,Mice, Inbred DBA ,Organ Specificity ,middle-t ,transgenic ,genetics/pathology, Gene Expression Regulation, Hair ,Carcinoma, Medullary ,Inbred C57BL, Mice ,abnormalities ,Genetically modified mouse ,medicine.medical_specialty ,Transgene ,Recombinant Fusion Proteins ,Mice, Transgenic ,Biology ,abnormalities, Humans, Mice, Mice ,Transgenic, Neoplasm ,Inbred DBA, Mice ,physiology, Recombinant Fusion Protein ,Thyroid carcinoma ,Antigen ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Thyroid Neoplasms ,neoplasms ,Molecular Biology ,chemistry/genetics/physiology, Binding Sites, Carcinoma ,Binding Sites ,Epidermal Growth Factor ,Wild type ,medicine.disease ,Molecular biology ,Mice, Inbred C57BL ,Endocrinology ,Gene Expression Regulation ,Vibrissae ,Polyomavirus Transforming ,biosynthesis/physiology, Sequence Deletion, Thyroid Neoplasm ,Carcinogenesis ,Hair - Abstract
Medullary thyroid carcinoma (MTC) is a rare human tumor affecting the calcitonin-secreting c-cells of the thyroid. Here we report that two independent strains of transgenic mice expressing a Polyomavirus (Py) truncated middle-T antigen (deltaMT), consisting of the amino-terminal 304 amino acids, and the full length Py small-T antigen, developed multifocal bilateral MTCs with 100\% penetrance. Occasionally one strain also developed mammary and bone tumors. Furthermore, offspring from both transgenic lines displayed pronounced waviness of the whiskers and fur, previously associated with defective epidermal growth factor receptor signaling. Transgene transcription, driven by the homologous early promoter/enhancer, and the corresponding translation products were detected in tumors and in many other organs which did not develop pathologies. The subcellular distribution of deltaMT and its interactions with the adapter proteins of the SHC family have also been analysed. Our study describes a novel murine model of MTC and provides evidence that the N-terminal 304 amino acid fragment of Py middle-T antigen, possibly in co-operation with small-T antigen, acts as a potent oncogene in c-cells of the thyroid.
- Published
- 1999