Altered expression of beta-catenin during radiation-induced colonic carcinogenesis.
Radiotherapy for malignant pelvic disease is commonly accompanied by treatment-induced proctitis, and rarely by colorectal cancer. Translocation of the beta-catenin protein, which is a key downstream effector of the Wnt signal transduction pathway, is frequently found in colorectal cancer. Nuclear beta-catenin enhances transcriptional activity of the cyclin D1 gene in cancer cells. Here, we evaluate the involvement of the Wnt pathway in radiation-induced colon carcinogenesis with rats (n = 36). Beta-catenin, APC, and cyclin D1 expression profiles were analyzed by immunohistochemistry in radiation-induced chronic colon injury including cancers and ulcerative lesions in rats (n = 12 in treated group, n = 12 in control group). In total, 3 cases of invasive adenocarcinomas were developed in the irradiated portion 50 weeks after a single dose of 36 Gy irradiation. Nuclear translocation of beta-catenin was observed in all radiation-induced colon cancers, whereas this protein was also found in the cytoplasm and/or nucleus of 9 cases of non-neoplastic irradiated colonocytes. Nuclear translocation of beta-catenin correlated with loss of APC and gain of cyclin D1 expression, suggesting activation of the Wnt pathway during radiation-induced colorectal carcinogenesis. A single dose of 10 Gy was also given for acute injury (n = 12: 3 each in days 0, 3, 5, and 7, respectively). Beta-catenin expression was distributed in the cytoplasm of degenerating glands at day 3 and 5, and was observed in the cell membrane of those glands with histological normalization at day 7 after irradiation. Because translocation of beta-catenin was found in irradiated-colonic mucosa as well as colon cancer, disruption of beta-catenin expression might be one of the early events in radiation-induced colonic carcinogenesis.
Nakashima
Masahiro
M
Tissue and Histopathology Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. moemoe@net-nagasaki-u.ac.jp
Meirmanov
Serik
S
Matsufuji
Reiko
R
Hayashida
Masayuki
M
Fukuda
Eiichiro
E
Naito
Shinji
S
Matsuu
Mutsumi
M
Shichijo
Kazuko
K
Kondo
Hisayoshi
H
Ito
Masahiro
M
Yamashita
Shunichi
S
Sekine
Ichiro
I
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D003092:Colitis / Q000378:metabolism; D003106:Colon / Q000473:pathology / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000528:radiation effects*; D005260:Female; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015534:Trans-Activators / Q000096:biosynthesis / Q000528:radiation effects*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin