Silencing of secreted frizzled-related protein genes in MSI colorectal carcinogenesis.
OBJECTIVE
The epigenetic pathway of colorectal carcinogenesis has recently become the focus of attention. The most common epigenetic change is the promoter hypermethylation of tumor suppressor genes. Secreted frizzled-related proteins have been identified and are reported to act as inhibitors of the Wnt signaling pathway. It has also been reported that microsatellite unstable cancers show more frequent hypermethylation in tumor suppressor genes and less frequent APC mutation.


METHODS
Fifty-one sporadic colorectal cancers were investigated, of which 22 were MSI-H and 29 were MSI-L/MSS. Methylation-specific polymerase chain reaction was performed to detect the methylation status of SFRP1, 2 and 5 genes.


RESULTS
All of the samples showed hypermethylation in the promoter region of SFRP1. MSI-H cancers showed more frequent hypermethylation in SFRP2 than MSI-L/MSS cancers, though there was no statistical significance. SFRP5 promoter hypermethylation was significantly more frequent in MSI-H cancers than in MSI-L/MSS cancers.


CONCLUSIONS
SFRPs may act as an important inhibitor of the Wnt signaling pathway in MSI-H cancers.
Tanaka
Junichiro
J
Department of Surgical Oncology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. jtan-tky@umin.ac.jp
Watanabe
Toshiaki
T
Kanazawa
Takamitsu
T
Tada
Tomohiro
T
Kazama
Yoshihiro
Y
Tanaka
Toshiaki
T
Nagawa
Hirokazu
H
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D053842:Microsatellite Instability; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C109618:SFRP2 protein, human; C118511:SFRP5 protein, human