title: RET receptor signaling: dysfunction in thyroid cancer and Hirschsprung's disease.
abstract: Gain-of-function mutations within the receptor tyrosine kinase gene RET cause inherited and non-inherited thyroid cancer. Somatic gene rearrangements of RET have been found in papillary thyroid carcinoma and germline point mutations in multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma (FMTC). Conversely, loss-of-function mutations are responsible for the development of Hirschsprung's disease, a congenital malformation of the enteric nervous system. Comparison between normal RET signaling activated by the RET ligand glial cell line-derived neurotrophic factor (GDNF) and abnormal RET signaling caused by various mutations has led to a deeper understanding of disease mechanisms. The focus of the present review is on recent progress in the study of RET signaling dysfunction in human diseases.
authors.affiliation: Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.forename: Mayumi
authors.initials: M
authors.lastname: Jijiwa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawai
authors.forename: Kengo
authors.initials: K
authors.lastname: Maeda
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ichiahara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human