title: CDX2 is mutated in a colorectal cancer with normal APC/beta-catenin signaling.
abstract: The majority of human colorectal cancers have elevated beta-catenin/TCF regulated transcription due to either inactivating mutations of the APC tumor suppressor gene or activating mutations of beta-catenin. Surprisingly, one commonly used colorectal cancer cell line was found to have intact APC and beta-catenin and no demonstrable beta-catenin/TCF regulated transcription. However, this line did possess a truncating mutation in one allele of CDX2, a gene whose inactivation has recently been shown to cause colon tumorigenesis in mice. Expression of CDX2 was found to be induced by restoring expression of wild type APC in a colorectal cancer cell line. These findings raise the intriguing possibility that CDX2 contributes to APC's tumor suppressive effects.
authors.affiliation: Program in Human Genetics and Molecular Biology, The Johns Hopkins University, Baltimore, Maryland, MD 21231, USA.
authors.forename: L T
authors.initials: LT
authors.lastname: da Costa
authors.forename: T C
authors.initials: TC
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: A B
authors.initials: AB
authors.lastname: Sparks
authors.forename: P J
authors.initials: PJ
authors.lastname: Morin
authors.forename: K
authors.initials: K
authors.lastname: Polyak
authors.forename: S
authors.initials: S
authors.lastname: Laken
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000483:Alleles; D000071616:CDX2 Transcription Factor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000071616:CDX2 Transcription Factor; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin