Down-regulation of E-cadherin and catenins in human pituitary growth hormone-producing adenomas.
Growth hormone (GH)-producing pituitary adenomas can be ultrastructurally divided into two major types: densely granulated and sparsely granulated. The latter type of adenoma characteristically exhibits globular accumulations of cytokeratin filaments known as fibrous bodies, which are immunohistochemically identifiable as juxtanuclear dot-like immunoreactivity. We hypothesize that the formation of fibrous body might be related to dysfunction of adhesion molecules, because of the functional relationship between intermediate filaments and the cadherin-catenin complex and frequent observation of loss of cohesiveness of the adenoma cells. Our recent immunohistochemical study showed that expression of E-cadherin and its undercoat proteins, alpha-, beta- and gamma-catenin, in GH cell adenomas with prominent fibrous bodies was significantly reduced compared with GH cell adenomas without fibrous bodies and the normal adenohypophysial cells. Although no mutation of exon 3 of the beta-catenin gene was found in any GH cell adenomas with fibrous bodies, methylation-specific polymerase chain reaction analysis revealed that the E-cadherin promoter region was methylated in 37.5% of these adenomas, two of which displayed total methylation, but not in GH cell adenomas without fibrous bodies. We conclude that the decreased expression of the E-cadherin-catenin complex and methylation of the E-cadherin gene promoter region are events associated with the formation of fibrous bodies in GH cell adenomas. It remains to be clarified to explain the mechanism by which down-regulation of adhesion molecules is involved in the abnormal assembly of intermediate filaments.
Department of Pathology, University of Tokushima School of Medicine, Tokushima, Japan. sano@basic.med.tokushima-u.ac.jp
Toshiaki
T
Sano
Qian Zhi
QZ
Rong
Noriko
N
Kagawa
Shozo
S
Yamada
D000236:Adenoma / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism*
D015820:Cadherins; D003598:Cytoskeletal Proteins; D013006:Growth Hormone