title: The TRK-T1 fusion protein induces neoplastic transformation of thyroid epithelium.
abstract: Genetic analysis of human papillary thyroid carcinomas (PTC) has revealed unique chromosomal translocations that form oncogenic fusion proteins and promote thyroid tumorigenesis in up to 60% of tumors examined. Although, the majority of thyroid specific translocations involve the growth factor receptor c-RET, variant rearrangements of the receptor for nerve growth factor, NTRK1 have also been described. One such translocation, TRK-T1, forms a fusion protein composed of the carboxyl terminal tyrosine kinase domain of NTRK1 and the amino terminal portion of TPR (Translocated Promoter Region). To determine if TRK-T1 expression can cause thyroid cancer in vivo, we developed transgenic mice that express the human TRK-T1 fusion protein in the thyroid. Immunohistochemical analysis of TRK-T1 transgenic mouse thyroids revealed TRK-T1 staining within the thyroid follicular epithelium. In contrast to nontransgenic littermates, 54% of transgenic mice developed thyroid abnormalities that included follicular hyperplasia and papillary carcinoma. Furthermore, all transgenic mice examined greater than 7 months of age developed thyroid hyperplasia and/or carcinoma. These data support the conclusion that TRK-T1 is oncogenic in vivo and contributes to the neoplastic transformation of the thyroid.
authors: Department of Otolaryngology, Head & Neck Surgery, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors: J P
authors: JP
authors: Russell
authors: D J
authors: DJ
authors: Powell
authors: M
authors: M
authors: Cunnane
authors: A
authors: A
authors: Greco
authors: G
authors: G
authors: Portella
authors: M
authors: M
authors: Santoro
authors: A
authors: A
authors: Fusco
authors: J L
authors: JL
authors: Rothstein
mesh_terms: D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D011519:Proto-Oncogenes; D051381:Rats; D011916:Rats, Inbred F344; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics*; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes; D014178:Translocation, Genetic
chemical_list: D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C073597:TPR protein, human; D013954:Thyroglobulin; D020917:Receptor, trkA