Loss of transgelin in repeated bouts of ulcerative colitis-induced colon carcinogenesis.
Though ulcerative colitis (UC)-associated colon cancer develops from dysplastic lesions caused by chronic inflammation, the specific mechanistic link between chronic inflammation and carcinogenesis in colon has not been integrated into molecular understanding. We therefore established an experimental animal model for colitic cancer, and used proteomic analysis, based on 2-DE and MALDI-TOF MS, to identify proteins involved in colitic cancer. In our model, 6-week-old C57BL/6J mice were exposed to 15 cycles of dextran sodium sulfate (DSS), with each cycle consisting of 0.7% DSS for 1 week followed by distilled water for 10 days. Colorectal tumors developed in 22 of 24 mice (91.6%), with a tumor multiplicity of 1.727 per tumor-bearing mouse. Comparative 2-DE analysis showed that 38 protein spots were differentially expressed in colon tumors and normal colon. We identified 27 of these proteins, including GRP94, HSC70, enolase, prohibitin, and transgelin. The reduction of transgelin expression in mouse colon tumors was confirmed by Western blotting and immunohistochemistry. We also found that transgelin expression was significantly reduced in human colon tumors compared with adjacent nontumorous tissues. In conclusion, these results suggest that loss of transgelin could be a candidate for biomarker of repeated colitis-associated colon cancer.
Yeo
Marie
M
Genome Research Center for Gastroenterology, Ajou University School of Medicine, Paldal-gu, Suwon, Korea.
Kim
Dong-Kyu
DK
Park
Hee Jin
HJ
Oh
Tae Young
TY
Kim
Jang Hee
JH
Cho
Sung Won
SW
Paik
Young-Ki
YK
Hahm
Ki-Baik
KB
D000818:Animals; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity; D015536:Down-Regulation; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin; D016264:Dextran Sulfate