Expression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2

• Published in: Oncogene Vol. 20; no. 35; pp. 4884 - 4890
• Main Authors: DANG, Duyen T, MAHATAN, Channing S, DANG, Long H, AGBOOLA, Iyabode A, YANG, Vincent W
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 09.08.2001; Nature Publishing Group
• Subjects: Adenomatous polyposis coli; beta Catenin; Biological and medical sciences; Biotechnology; Cancer; CDX2 protein; CDX2 Transcription Factor; Cell cycle; Cell growth; Cell physiology; Cell proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Colon cancer; Colonic Neoplasms - genetics; Colorectal cancer; Cyclin-dependent kinases; Cytoskeletal Proteins - physiology; Digestive system; DNA-Binding Proteins - genetics; Familial adenomatous polyposis; Fundamental and applied biological sciences. Psychology; Gastrointestinal tract; Gene mutations; Gene therapy; Genes, APC; Genetic aspects; Genetic disorders; Genetic research; Health. Pharmaceutical industry; HMGB Proteins; Homeobox; Homeodomain Proteins - physiology; Humans; Industrial applications and implications. Economical aspects; Intestine; Kinases; KLF4 protein; Kruppel-Like Transcription Factors; Medical research; Medicine; Medicine, Experimental; Molecular and cellular biology; Mutation; Phenotypes; Polyposis coli; Promoter Regions, Genetic; RNA, Messenger - analysis; Signal transduction; Surveys; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 1 Protein; Transcription factors; Transcription Factors - genetics; Tumor cell lines; Tumor Cells, Cultured; Tumor suppressor genes; Tumors; Zinc finger proteins; β-Catenin; United States > US; Maryland; Baltimore Maryland; Human; Tumor; Colon; Gene expression; Gene therapy; Genetic transfer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204645

Gut-enriched Krüppel-like factor (GKLF or KLF4) is a zinc finger-containing, epithelial-specific transcription factor, that functions as a suppressor of cell proliferation. We previously showed that GKLF expression is decreased in intestinal and colonic adenomas, respectively, from multiple intestinal neoplasia (Min) mice and familial adenomatous polyposis (FAP) patients. This study shows that GKLF is induced upon activation of the adenomatous polyposis coli (APC) gene. However, among several human colon cancer cell lines surveyed, expression of GKLF is lowest in RKO, a line with wild-type APC and beta-catenin. RKO contains a mutated allele that encodes the putative tumor suppressor homeodomain protein, CDX2. We show that wild-type CDX2 activates the GKLF promoter and that the mutated CDX2 has a dominant negative effect on wild-type function. Our results may help explain the exceedingly low levels of GKLF expression detected in this cell line, which may in turn contribute to the tumor phenotype.