Infrequent mutation of APC, AXIN1, and GSK3B in human pituitary adenomas with abnormal accumulation of CTNNB1.
We analyzed mutation of the APC, AXIN1, and GSK3genes in 14 pituitary adenomas with abnormal nuclear accumulations of CTNNB1. These tumors did not harbor mutation of the CTNNB1 gene. The genes analyzed encode proteins associated with ubiquitin-mediated degradation of CTNNB1. Although the regions encoding functional domains of these protein products were analyzed, no significant genetic alterations were found. Furthermore, the antibody for the C-terminus of APC detected normal expression of the APC protein in these pituitary adenomas. Our present results imply that an unknown mechanism(s) accelerates the accumulation of CTNNB1 that plays an important role in the pathogenesis of human pituitary adenomas. However, the possibility that mutation of regions outside of our survey or epigenetic mechanism play an important role cannot be excluded.
Sun
Chunlan
C
Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. horii@mail.tains.tohoku.ac.jp
Yamato
Takashi
T
Kondo
Emiko
E
Furukawa
Toru
T
Ikeda
Hidetoshi
H
Horii
Akira
A
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D000368:Aged; D060466:Axin Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D051176:beta Catenin
C555451:AXIN1 protein, human; D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3