Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers.
The beta-catenin pathway plays a central role in transcriptional signaling and cell-cell interactions in colonic epithelium. Alterations of the expression of beta-catenin, and its binding partners E-cadherin and the adenomatous polyposis coli protein (APC), are frequent events in sporadic colorectal cancer. Ulcerative colitis (UC)-related cancers originate in a field of chronic inflammation and therefore may have different alterations in the beta-catenin pathway than sporadic cancers. To test this hypothesis, expression and subcellular localization of beta-catenin, E-cadherin, and APC were detected by immunohistochemistry in paraffin sections from 33 UC-related and 42 sporadic colorectal cancers. Although beta-catenin and E-cadherin expression were predominantly limited to the lateral cell membrane in normal colonic epithelium, both tumor groups showed an overall shift from membranous to cytoplasmic expression for these proteins. An increase in nuclear localization of beta-catenin and a decrease in cytoplasmic APC expression also were seen in both cancer groups compared with normal epithelium. Abnormal beta-catenin expression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal beta-catenin expression was more closely linked to APC alterations in sporadic cancers than in UC-related cancers. These data suggest that alterations of the beta-catenin pathway are important in both UC-related and sporadic colorectal cancers. However, differences in the expression patterns of beta-catenin, E-cadherin, and APC between UC-related and sporadic colorectal cancers suggest that the specific alterations in this pathway may differ in these two cancer groups.
Aust
D E
DE
Cancer Center, University of California San Francisco, 94143-0808, USA.
Terdiman
J P
JP
Willenbucher
R F
RF
Chew
K
K
Ferrell
L
L
Florendo
C
C
Molinaro-Clark
A
A
Baretton
G B
GB
Löhrs
U
U
Waldman
F M
FM
D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000033:anatomy & histology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D015534:Trans-Activators; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin