Cdx1 homeobox gene during human colon cancer progression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-09

AUTHORS

Claire Domon-Dell, Anne Schneider, Virginie Moucadel, Eric Guerin, Dominique Guenot, Sarah Aguillon, Isabelle Duluc, Elisabeth Martin, Juan Iovanna, Jean-François Launay, Bernard Duclos, Marie-Pierre Chenard, Christian Meyer, Pierre Oudet, Michèle Kedinger, Marie-Pierre Gaub, Jean-Noël Freund

ABSTRACT

The Cdx1 homeobox gene encodes an intestine-specific transcription factor with a pro-oncogenic function in vitro. Here we have analysed the pattern of Cdx1 in human colon cancer progression. Cdx1 expression remains at a high level in the majority of the polyps and it is even overexpressed in more than one-third of the specimens, consistent with the fact that the gene is an intestine-specific target of oncogenic pathways. However, Cdx1 decreases in one-fifth of the polyps, which is reminiscent of the loss of expression previously reported in the majority of carcinomas. Allelic imbalance analysis demonstrates that the Cdx1 locus located on chromosome 5q is a major site of genomic rearrangement in colorectal cancers, and that the frequency of the rearrangements increases during polyps to carcinoma progression. Allelic imbalance at the Cdx1 locus occurs in relation to, although not invariably in association with, the rearrangements at the APC locus on the same chromosomal arm. Xenografts of primary human colon carcinomas indicate that the level of Cdx1 mRNA correlates with the intensity of allelic imbalance. Together, these data show that Cdx1 exhibits a complex pattern during colorectal cancer progression. Given that Cdx1 has a pro-oncogenic function in vitro, the maintenance of a high level of expression in polyps, and even its overexpression in one-third of the specimens, suggest that this homeobox gene may be an important factor in the process toward malignant transformation during the first steps of tumorigenesis. More... »

PAGES

1206756

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1206756

DOI

http://dx.doi.org/10.1038/sj.onc.1206756

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015471998

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12970739


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