Journal
ONCOGENE
Volume 20, Issue 35, Pages 4884-4890Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204645
Keywords
gut-enriched Kruppel-like factor; Kruppel-like factor 4; colon cancer; CDX2; adenomatous polyposis coli; dominant negative
Funding
- NCI NIH HHS [R01 CA084197, CA84197, R01 CA084197-02] Funding Source: Medline
- NIDDK NIH HHS [R01 DK052230-04, F32 DK010020, R01 DK052230, DK10020, DK52230] Funding Source: Medline
Ask authors/readers for more resources
Gut-enriched Kruppel-like factor (GKLF or KLF4) is a zinc finger-containing, epithelial-specific transcription factor, that functions as a suppressor of cell proliferation. We previously showed that GKLF expression is decreased in intestinal and colonic adenomas, respectively, from multiple intestinal neoplasia (Min) mice and familial adenomatous polyposis (FAP) patients. This study shows that GKLF is induced upon activation of the adenomatous polyposis coli (APC) gene. However, among several human colon cancer cell lines surveyed, expression of GKLF is lowest in RKO, a line with wildtype APC and beta -catenin. RKO contains a mutated allele that encodes the putative tumor suppressor homeodomain protein, CDX2. We show that wild-type CDX2 activates the GKLF promoter and that the mutated CDX2 has a dominant negative effect on wild-type function. Our results may help explain the exceedingly low levels of GKLF expression detected in this cell line, which may in turn contribute to the tumor phenotype.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available