ID 111694
Title Alternative
MUTATIONS OF RET AND GDNF GENES IN PITUITARY ADENOMAS
Author
Tanaka, Chisato The University of Tokushima KAKEN Search Researchers
Moritani, Maki The University of Tokushima
Shimizu, Eiji The University of Tokushima
Yamaoka, Takashi The University of Tokushima
Yamada, Shozo Toranomon Hospital
Keywords
RET proto-oncogene
Glial cell line-derived neurotrophic factor (GDNF) gene
Mutations
Expression
Pituitary adenomas
Content Type
Journal Article
Description
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-α (GDNFR-α). 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.
Journal Title
Endocrine Journal
ISSN
13484540
09188959
NCID
AA12020190
AA10901436
Publisher
The Japan Endocrine Society
Volume
46
Issue
1
Start Page
199
End Page
207
Published Date
1999
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences
University Hospital
Medical Sciences
Institute of Advanced Medical Sciences