C-cell and thyroid epithelial tumours and altered follicular development in transgenic mice expressing the long isoform of MEN 2A RET
| Autor: | Bruce A.J. Ponder, Kenneth Jones, Lucinda F. Reynolds, Darrin P. Smith, Louise Howard, Douglas J. Winton, Carol Houghton, Aaron N. Cranston |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Calcitonin
Genetically modified mouse endocrine system Cancer Research medicine.medical_specialty DNA Complementary endocrine system diseases RNA Splicing Recombinant Fusion Proteins Cystadenocarcinoma Mutation Missense Mice Transgenic Multiple Endocrine Neoplasia Type 2a Biology medicine.disease_cause Thyroid carcinoma Mice Proto-Oncogene Proteins Internal medicine Ultimopharyngeal body Genes Synthetic Genetics medicine Animals Drosophila Proteins Protein Isoforms Thyroid Neoplasms Transgenes Promoter Regions Genetic Molecular Biology Mutation Proto-Oncogene Proteins c-ret Thyroid Receptor Protein-Tyrosine Kinases Carcinoma Papillary Gene Expression Regulation Neoplastic Pancreatic Neoplasms Cell Transformation Neoplastic Endocrinology medicine.anatomical_structure Amino Acid Substitution Carcinoma Medullary PAX8 Carcinogenesis |
| Zdroj: | Oncogene. 20:3986-3994 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1204434 |
| Popis: | Gain-of-function mutations in the gene encoding the receptor tyrosine kinase RET have been identified as the aetiological factor for multiple endocrine neoplasia type 2A (MEN2A). MEN2A is a dominantly-inherited cancer predisposition syndrome characterized by medullary thyroid carcinoma, a tumour of the calcitonin-producing thyroid C-cells. There are three isoforms of RET: RET9, RET43 and RET51, and although in vitro evidence suggests they vary in cellular transformation activities, little is known about their function in tumorigenesis in vivo. To address this, we used RET51 cDNA to construct mice in which the most frequent MEN2A mutation, Cys-634-Arg, was expressed under the control of the human calcitonin promoter (CT-2A mice). These mice developed C-cell tumours resembling human MTC and follicular tumours resembling human papillary thyroid carcinoma (PTC) depending on the founder line examined. One founder line developed compound MTC/PTC at low frequency (8%) and pancreatic cystadenocarcinoma. CT-2A mice also displayed a developmental defect in thyroid follicular structure, in which much of the thyroid was occupied by large irregular cystic follicles thought to be derived from the ultimobranchial body, a developmental precursor of the thyroid gland. The CT-2A mice will provide a suitable model to further study the effects of the MEN 2A RET mutation in vivo. |
| Databáze: | OpenAIRE |
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