The TRK-T1 fusion protein induces neoplastic transformation of thyroid

John P. Russell, Daniel J. Powell, Mary Cunnane, Angela Greco, Giuseppe Portella, Massimo Santoro, Alfredo Fusco, Jay L. Rothstein

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5729-5735
Number of pages7
JournalOncogene
Volume19
Issue number50
Publication statusPublished - Nov 23 2000

Keywords

  • Neoplasia
  • Nerve growth factor receptor
  • Papillary thyroid carcinoma
  • RET/PTC
  • Transgenic mice
  • TRK-T1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint

Dive into the research topics of 'The TRK-T1 fusion protein induces neoplastic transformation of thyroid'. Together they form a unique fingerprint.

Cite this