在具有β-连环蛋白（CTNNB1）异常积聚的人垂体腺瘤中，腺瘤性息肉病基因（APC）、轴抑制蛋白1（AXIN1）和糖原合成酶激酶3β（GSK3B）的突变频率较低。

Infrequent mutation of APC, AXIN1, and GSK3B in human pituitary adenomas with abnormal accumulation of CTNNB1.

作者信息

Sun Chunlan, Yamato Takashi, Kondo Emiko, Furukawa Toru, Ikeda Hidetoshi, Horii Akira

机构信息

Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.

出版信息

J Neurooncol. 2005 Jun;73(2):131-4. doi: 10.1007/s11060-004-4597-3.

DOI:10.1007/s11060-004-4597-3

PMID:15981102

Abstract

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.

摘要

我们分析了14例β-连环蛋白（CTNNB1）核内异常聚集的垂体腺瘤中腺瘤性息肉病基因（APC）、轴抑制蛋白1（AXIN1）和糖原合成酶激酶3（GSK3）基因的突变情况。这些肿瘤未发生CTNNB1基因突变。所分析的基因编码与泛素介导的CTNNB1降解相关的蛋白质。尽管对这些蛋白质产物功能结构域的编码区域进行了分析，但未发现明显的基因改变。此外，APC C末端抗体检测到这些垂体腺瘤中APC蛋白表达正常。我们目前的结果表明，一种未知机制加速了CTNNB1的聚集，而CTNNB1在人类垂体腺瘤发病机制中起重要作用。然而，不能排除我们所检测区域以外的基因突变或表观遗传机制起重要作用的可能性。