Analysis of the β‐Catenin/T Cell Factor Signaling Pathway in 36 Gastrointestinal and Liver Cancer Cells

• Published in: Cancer science 2002-11, Vol.93 (11), p.1213-1220
• Main Authors: Ikenoue, Tsuneo, Ijichi, Hideaki, Kato, Naoya, Kanai, Fumihiko, Masaki, Tsutomu, Rengifo, William, Okamoto, Makoto, Matsumura, Masayuki, Kawabe, Takao, Shiratori, Yasushi, Omata, Masao
• Format: Article
• Language: English
• Subjects: Adenomatous polyposis coli; Antigen-presenting cells; APC; beta Catenin; Carcinoma, Hepatocellular - etiology; Catenin; Cell activation; Colon; Colorectal Neoplasms - etiology; Cytoskeletal Proteins - analysis; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - physiology; DNA-Binding Proteins - analysis; DNA-Binding Proteins - physiology; Electrophoretic mobility; Gastric cancer; Gastrointestinal cancer; Genes, APC; GSK‐3β; Hepatocellular carcinoma; Hepatocytes; Humans; Immunohistochemistry; Kinases; Liver cancer; Liver Neoplasms - etiology; Lymphocytes T; Lymphoid Enhancer-Binding Factor 1; Mutation; Pancreatic cancer; Polyposis coli; Signal transduction; Stomach Neoplasms - etiology; T cell factor; Trans-Activators - analysis; Trans-Activators - genetics; Trans-Activators - physiology; Transcription Factors - analysis; Transcription Factors - physiology; Tumor cell lines; Tumor Cells, Cultured; Up-Regulation; β‐Catenin
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.2002.tb01226.x

We investigated the frequency and mechanism of |bT‐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 β‐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 β‐catenin, and Tcf‐4 was highly expressed in these cell lines with upregulated signaling. Nuclear β‐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 β‐catenin suggests the involvement of other mechanisms than mutations of APC or β‐catenin.