Aberrant expression and phosphorylation of β-catenin in human colorectal cancer

被引:81
作者
Takayama, T
Shiozaki, H
Doki, Y
Oka, H
Inoue, M
Yamamoto, M
Tamura, S
Shibamoto, S
Ito, F
Monden, M
机构
[1] Osaka Univ, Sch Med, Dept Surg 2, Osaka 565, Japan
[2] Setsunan Univ, Fac Pharmaceut Sci, Dept Biochem, Osaka 57301, Japan
关键词
beta-catenin; tyrosine phosphorylation; colorectal cancer;
D O I
10.1038/bjc.1998.97
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The cytoplasmic domain of cadherins is known to associate with the intracellular proteins, catenins, which link cadherins to the actin-based cytoskeleton. In this study, we immunohistochemically investigated the expression of beta-catenin as well as E-cadherin and alpha-catenin in 86 human colorectal cancers, and we analysed their coexpression pattern and relationship to clinicopathological factors. In cancerous tissues, the frequency of reduced expression of beta-catenin (28 of 86, 33%,) was similar to that of E-cadherin (19 of 86, 22%), but less than that of alpha-catenin (47 of 86, 55%). All three molecules were expressed strongly, as was the normal epithelium, in 36 cases (42%), whereas the rest (50 cases, 58%) showed reduction in one of the molecules. The reduction of beta-catenin expression was significantly correlated with dedifferentiation, Duke's stage, lymph node metastasis and liver metastasis. Next, we examined tyrosine phosphorylation in the protein complex immunoprecipitated with E-cadherin, as E-cacherin function is down-regulated by receptor-type tyrosine kinase in vitro. It was of interest that up-regulation of tyrosine phosphorylation of beta-catenin was more frequently observed in cancerous tissues than in the matching normal mucosa. These results suggest that beta-catenin may have important regulatory roles within an E-cadherin-mediated adhesion system in human colorectal cancers.
引用
收藏
页码:605 / 613
页数:9
相关论文
共 45 条
[1]  
ABERLE H, 1994, J CELL SCI, V107, P3655
[2]   LOSS OF EPITHELIAL DIFFERENTIATION AND GAIN OF INVASIVENESS CORRELATES WITH TYROSINE PHOSPHORYLATION OF THE E-CADHERIN BETA-CATENIN COMPLEX IN CELLS TRANSFORMED WITH A TEMPERATURE-SENSITIVE V-SRC GENE [J].
BEHRENS, J ;
VAKAET, L ;
FRIIS, R ;
WINTERHAGER, E ;
VANROY, F ;
MAREEL, MM ;
BIRCHMEIER, W .
JOURNAL OF CELL BIOLOGY, 1993, 120 (03) :757-766
[3]  
Candidus S, 1996, CANCER RES, V56, P49
[4]   The classification of cancer of the rectum [J].
Dukes, CE .
JOURNAL OF PATHOLOGY AND BACTERIOLOGY, 1932, 35 (03) :323-332
[5]   THE SPREAD OF RECTAL CANCER AND ITS EFFECT ON PROGNOSIS [J].
DUKES, CE ;
BUSSEY, HJR .
BRITISH JOURNAL OF CANCER, 1958, 12 (03) :309-&
[6]   ENHANCED SURVIVAL OF PATIENTS WITH COLON AND RECTAL-CANCER IS BASED UPON WIDE ANATOMIC RESECTION [J].
ENKER, WE ;
LAFFER, UT ;
BLOCK, GE .
ANNALS OF SURGERY, 1979, 190 (03) :350-360
[7]   EMBRYONIC AXIS INDUCTION BY THE ARMADILLO REPEAT DOMAIN OF BETA-CATENIN - EVIDENCE FOR INTRACELLULAR SIGNALING [J].
FUNAYAMA, N ;
FAGOTTO, F ;
MCCREA, P ;
GUMBINER, BM .
JOURNAL OF CELL BIOLOGY, 1995, 128 (05) :959-968
[8]   P60(V-SRC) CAUSES TYROSINE PHOSPHORYLATION AND INACTIVATION OF THE N-CADHERIN CATENIN CELL-ADHESION SYSTEM [J].
HAMAGUCHI, M ;
MATSUYOSHI, N ;
OHNISHI, Y ;
GOTOH, B ;
TAKEICHI, M ;
NAGAI, Y .
EMBO JOURNAL, 1993, 12 (01) :307-314
[9]   WNT-1 MODULATES CELL-CELL ADHESION IN MAMMALIAN-CELLS BY STABILIZING BETA-CATENIN BINDING TO THE CELL-ADHESION PROTEIN CADHERIN [J].
HINCK, L ;
NELSON, WJ ;
PAPKOFF, J .
JOURNAL OF CELL BIOLOGY, 1994, 124 (05) :729-741
[10]  
Inomata M, 1996, CANCER RES, V56, P2213