RET receptor signaling: dysfunction in thyroid cancer and Hirschsprung's disease.
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.
Asai
Naoya
N
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Jijiwa
Mayumi
M
Enomoto
Atsushi
A
Kawai
Kumi
K
Maeda
Kengo
K
Ichiahara
Masatoshi
M
Murakumo
Yoshiki
Y
Takahashi
Masahide
M
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*
D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human