The homeodomain transcription factor Cdx1 does not behave as an oncogene in normal mouse intestine.
The Caudal-related homeobox genes Cdx1 and Cdx2 are intestine-specific transcription factors that regulate differentiation of intestinal cell types. Previously, we have shown Cdx1 to be antiproliferative and to promote cell differentiation. However, other studies have suggested that Cdx1 may be an oncogene. To test for oncogenic behavior, we used the murine villin promoter to ectopically express Cdx1 in the small intestinal villi and colonic surface epithelium. No changes in intestinal architecture, cell differentiation, or lineage selection were observed with expression of the transgene. Classic oncogenes enhance proliferation and induce tumors when ectopically expressed. However, the Cdx1 transgene neither altered intestinal proliferation nor induced spontaneous intestinal tumors. In a murine model for colitis-associated cancer, the Cdx1 transgene decreased, rather than increased, the number of adenomas that developed. In the polyps, the expression of the endogenous and the transgenic Cdx1 proteins was largely absent, whereas endogenous Villin expression was retained. This suggests that transgene silencing was specific and not due to a general Villin inactivation. In conclusion, neither the ectopic expression of Cdx1 was associated with changes in intestinal cell proliferation or differentiation nor was there increased intestinal cancer susceptibility. Our results therefore suggest that Cdx1 is not an oncogene in normal intestinal epithelium.
Crissey
Mary Ann S
MA
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 600 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104 USA.
Guo
Rong-Jun
RJ
Fogt
Franz
F
Li
Hong
H
Katz
Jonathan P
JP
Silberg
Debra G
DG
Suh
Eun Ran
ER
Lynch
John P
JP
D000818:Animals; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D000071616:CDX2 Transcription Factor; C491272:Cdx1 protein, mouse; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors