Claudin-1 protein is a major factor involved in the tumorigenesis of colorectal cancer.
BACKGROUND
The molecular and morphological alterations of the tight junctions in colorectal cancer (CRC) are still poorly understood. The possible involvement of claudin-1 (CL-1), one of the major tight junctional proteins (TJPs), was investigated in the tumorigenesis of CRC.


METHODS
Adenocarcinoma tissue and paired normal mucosa specimens were resected from surgical specimens of CRC patients and analyzed to determine whether the expression of CL-1 correlated with the clinicopathological factors and to determine the role of CL-1 in the alteration of tight junctions during tumorigenesis.


RESULTS
The expression of CL-1 at the mRNA and protein levels was analyzed in 41 cases and was found to increase in the CRC tissue in comparison to that in the normal tissue specimens. The mRNA levels of CL-1 were correlated with tumor depth, but not with the preoperative carcinoembryonic antigen (CEA) serum level. When T84 cells, a human colon cancer cell line, were transfected with the CL-1 gene, the CL-1 overexpressing cells grew as aggregates in contrast to the monolayer formation of the parental cells. In addition, trypsin-treated CL-1 overexpressing cells aggregated more easily than did the parental cells.


CONCLUSIONS
CL-1 plays a pivotal role in cell morphology and behavior in the colonic epithelium. CL-1 protein may therefore be one of the major factors involved in the tumorigenesis of CRC.
Department of Biochemistry, Faculty of Medicine, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan.
Qun
Q
Huo
Tetsushi
T
Kinugasa
Lin
L
Wang
Jian
J
Huang
Jun
J
Zhao
Hirotomo
H
Shibaguchi
Motomu
M
Kuroki
Toshihiro
T
Tanaka
Yuichi
Y
Yamashita
Kazuki
K
Nabeshima
Hiroshi
H
Iwasaki
Masahide
M
Kuroki
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D049109:Cell Proliferation; D062445:Claudin-1; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; D012333:RNA, Messenger