Analysis of the beta-catenin/T cell factor signaling pathway in 36 gastrointestinal and liver cancer cells.
We investigated the frequency and mechanism of beta-catenin/T cell factor (Tcf) signaling activation in a panel of 36 human gastrointestinal and liver cancer cell lines. Reporter assay and electrophoretic mobility shift assay revealed that the beta-catenin/Tcf signaling was upregulated in 12 of 12 (100%) colorectal, 5 of 8 (68%) gastric, 2 of 7 (29%) hepatic, and none of 9 pancreatic cancer cell lines. The activation of the pathway was mainly due to the mutation of adenomatous polyposis coli (APC) or beta-catenin, and Tcf-4 was highly expressed in these cell lines with upregulated signaling. Nuclear beta-catenin was observed not only in the signaling-activated cell lines, but also in 14 of 25 (56%) primary gastric cancers, 15 of 20 (75%) colon cancers, 5 of 19 (26%) hepatocellular carcinomas, and none of 13 pancreatic cancers. The presence of signaling-upregulated gastric cancer cell lines with intact APC and beta-catenin suggests the involvement of other mechanisms than mutations of APC or beta-catenin.
Ikenoue
Tsuneo
T
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan. t-ikenoue@asahi-life.or.jp
Ijichi
Hideaki
H
Kato
Naoya
N
Kanai
Fumihiko
F
Masaki
Tsutomu
T
Rengifo
William
W
Okamoto
Makoto
M
Matsumura
Masayuki
M
Kawabe
Takao
T
Shiratori
Yasushi
Y
Omata
Masao
M
D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D015179:Colorectal Neoplasms / Q000209:etiology*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000209:etiology*; D051821:Lymphoid Enhancer-Binding Factor 1; D013274:Stomach Neoplasms / Q000209:etiology*; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin