CDX2 is mutated in a colorectal cancer with normal APC/beta-catenin signaling.
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.
da Costa
L T
LT
Program in Human Genetics and Molecular Biology, The Johns Hopkins University, Baltimore, Maryland, MD 21231, USA.
He
T C
TC
Yu
J
J
Sparks
A B
AB
Morin
P J
PJ
Polyak
K
K
Laken
S
S
Vogelstein
B
B
Kinzler
K W
KW
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
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