Expression of tight and adherens junction proteins in ulcerative colitis associated colorectal carcinoma: upregulation of claudin-1, claudin-3, claudin-4, and beta-catenin.
BACKGROUND
Tight junction (TJ) proteins play a critical role in cellular adhesion, glandular differentiation, and cellular proliferation. The function of these proteins is compromised in a number of intestinal diseases, including ulcerative colitis that has an increased incidence for colorectal carcinoma (CAC). The aim of this study was to determine the expression of TJ proteins, claudin-1-4, occludin, ZO-1, and the adherens junction (AJ) protein beta-catenin in CAC.


METHODS
Sixteen colectomy specimens with CAC, adjoining intraepithelial neoplasia, and normal mucosa were studied by immunofluorescence. A semiquantitative evaluation of all investigated proteins was performed by scoring the staining intensity, and the TJ and AJ protein expression in neoplastic cells was compared to normal and intraepithelial neoplastic colonic mucosa.


RESULTS
Using an intensity scoring system, mucosa of crypts and surfaces of CAC exhibited significantly elevated expression levels of claudin-1, claudin-3, claudin-4, and beta-catenin compared to intraepithelial neoplasia and normal mucosa (p<0.05). These data were confirmed by a comparative score. The expression of claudin-2, occludin, and ZO-1 showed no differences between the groups.


CONCLUSIONS
TJ proteins claudin-1, claudin-3, claudin-4, and the AJ protein beta-catenin are overexpressed in CAC. This suggests that these proteins may become potential markers and targets in CAC.
Mees
S T
ST
Department of General and Visceral Surgery, University Hospital of Muenster, 48149 Muenster, Germany.
Mennigen
R
R
Spieker
T
T
Rijcken
E
E
Senninger
N
N
Haier
J
J
Bruewer
M
M
D022005:Adherens Junctions / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000378:metabolism; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D003093:Colitis, Ulcerative / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003710:Demography; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D019108:Tight Junctions / Q000378:metabolism*; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D008565:Membrane Proteins; D051176:beta Catenin