Increased claudin-1 protein expression contributes to tumorigenesis in ulcerative colitis-associated colorectal cancer.
BACKGROUND
The molecular and morphological alterations of the tight junctions in ulcerative colitis (UC)-associated colorectal cancer are still poorly understood. The possible involvement of claudin-1 (CL-1), one of the major tight junctional proteins, was investigated in the tumorigenesis of UC-associated CRC.


METHODS
A total of 39 patients with UC underwent surgical treatment from January 2001 until October 2009 at Kurume University Hospital in Fukuoka. CRC tissue specimens were analyzed to determine whether the expression of CL-1 correlates with clinicopathological factors and to determine the role of CL-1 and β-catenin in the alteration of tight junctions during tumorigenesis.


RESULTS
The operations were 30 of elective surgery and 9 of emergency surgery. Colectomy was performed in five patients (12.8%) because of UC-associated CRC, and in another patient (2.6 %) because of high-grade dysplasia. The immunostaining pattern of the high-grade dysplasia and UC-associated CRC for CL-1 showed much stronger and more diffuse staining in comparison to the normal or UC colonic mucosa. The expression of β-catenin was also positive or up-regulated in all of the UC-associated CRC and high-grade dysplasia tissue specimens.


CONCLUSIONS
These observations suggested that CL-1 plays a pivotal role in the regulation of cellular morphology and behavior in UC. We speculate that increased CL-1 expression may be involved in the early stages of transformation in UC-associated neoplasia. CL-1 protein may therefore be a good candidate for surveillance of patients with UC.
Kinugasa
Tetsushi
T
Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. kinugasa_tetsushi@med.kurume-u.ac.jp
Akagi
Yoshito
Y
Yoshida
Takefumi
T
Ryu
Yasuhiko
Y
Shiratuchi
Ichitarou
I
Ishibashi
Nobuya
N
Shirouzu
Kazuo
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D062445:Claudin-1; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D055815:Young Adult
C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins