Cdx1, a dispensable homeobox gene for gut development with limited effect in intestinal cancer

• Published in: Oncogene Vol. 27; no. 32; pp. 4497 - 4502
• Main Authors: Bonhomme, C, Calon, A, Martin, E, Robine, S, Neuville, A, Kedinger, M, Domon-Dell, C, Duluc, I, Freund, J-N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.07.2008; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Animal models; Animals; Apoptosis; Azoxymethane; Azoxymethane - toxicity; Cancer; CDX2 protein; CDX2 Transcription Factor; Cell Biology; Cell differentiation; Cell proliferation; Colorectal cancer; Embryos; Epithelium; Gastrointestinal cancer; Gene expression; Genes, APC; Genes, Homeobox; Genetic aspects; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Human Genetics; Internal Medicine; Intestinal Neoplasms - etiology; Intestinal Neoplasms - genetics; Intestine; Intestines; Intestines - embryology; Life Sciences; Malignancy; Medicine; Medicine & Public Health; Mice; Mice, Transgenic; Oncology; Pathology; Physiological aspects; Risk factors; Rodents; short-communication; Transcription Factors - physiology; Transgenic mice; Tumorigenesis; Tumors; Villus; France; mouse; development; cancer; intestine
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2008.78

The homeobox gene Cdx1 is involved in anteroposterior patterning in embryos and its expression selectively persists in the intestinal epithelium throughout life. In human colon cancers, Cdx1 is overexpressed in few cases and lost in the majority of adenocarcinomas. We used mouse models of gain and loss-of-function to investigate the role of Cdx1 in intestinal development and cancers. Transgenic mice overexpressing Cdx1 and knockout mice exhibited a morphologically normal intestine. Cell proliferation, specification into the four differentiated lineages and migration along the crypt-villus axis were unchanged compared to wild-type mice. Changing Cdx1 caused an inverse and dose-dependent modification of the expression of the paralogous gene Cdx2 , indicating that Cdx1 fine-tunes Cdx2 activity. Transgenenic and knockout mice failed to spontaneously develop tumours. Overexpressing Cdx1 was without incidence on the frequency of intestinal tumours induced chemically by azoxymethane treatment or genetically in Apc Δ14/+ mice. However, it augmented the severity of the tumours in Apc Δ14/+ mice. Inversely, the loss-of-function of Cdx1 in knockout mice was without incidence on the growth of tumours induced by azoxymethane. We conclude that Cdx1 is dispensable for intestinal development and that its overexpression could increase malignancy in early stages of tumourigenesis.