RRC ID 62147
Author Yoshimoto K, Tanaka C, Moritani M, Shimizu E, Yamaoka T, Yamada S, Sano T, Itakura M.
Title Infrequent detectable somatic mutations of the RET and glial cell line-derived neurotrophic factor (GDNF) genes in human pituitary adenomas.
Journal Endocr J
Abstract RET is a receptor tyrosine kinase expressed in neuroendocrine cells and tumors. RET is activated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF receptor-alpha (GDNFR-alpha). Activating mutations of the RET proto-oncogene were found in multiple endocrine neoplasia (MEN) 2 and in sporadic medullary thyroid carcinoma and pheochromocytoma of neuroendocrine origin. Mutations of the RET proto-oncogene and the glial cell line-derived neurotrophic factor (GDNF) gene were examined in human pituitary tumors. No mutations of the RET proto-oncogene including the cysteine-rich region or codon 768 and 918 in the tyrosine kinase domain were detected in 172 human pituitary adenomas either by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) or by PCR-restriction fragment length polymorphism (RFLP). Further, somatic mutations of the GDNF gene in 33 human pituitary adenomas were not detected by PCR-SSCP. One polymorphism of the GDNF gene at codon 145 of TGC or TGT was observed in a prolactinoma. The RET proto-oncogene message was detected in a normal human pituitary gland or 4 of 4 human pituitary adenomas with reverse transcription (RT)-PCR, and in rodent pituitary tumor cell lines with Western blotting. The expression of GDNF gene was detected in 1 of 4 human somatotroph adenomas, 1 of 2 corticotroph adenomas, and 2 of 6 rodent pituitary tumor cell lines with RT-PCR. Based on these, it is concluded that somatic mutations of the RET proto-oncogene or the GDNF gene do not appear to play a major role in the pituitary tumorigenesis in examined tumors.
Volume 46(1)
Pages 199-207
Published 1999-2-1
DOI 10.1507/endocrj.46.199
PMID 10426588
MeSH Adenoma / genetics* Animals DNA Mutational Analysis Drosophila Proteins* Gene Expression Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Humans Mice Mutation* Nerve Growth Factors* Nerve Tissue Proteins / genetics* Pituitary Neoplasms / genetics* Proto-Oncogene Mas Proto-Oncogene Proteins / genetics* Proto-Oncogene Proteins c-ret RNA, Neoplasm / analysis Rats Receptor Protein-Tyrosine Kinases / genetics* Reverse Transcriptase Polymerase Chain Reaction
IF 1.952
Resource
Human and Animal Cells MtT/S(RCB0528) MtT/SM(RCB0530)