Open AccessExpression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2
Author(s) -
Duyen T. Dang,
Channing S. Mahatan,
Long H. Dang,
Iyabode A Agboola,
Vincent W. Yang
Publication year - 2001
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/sj.onc.1204645
Subject(s) - klf4 , krüppel , adenomatous polyposis coli , biology , cdx2 , familial adenomatous polyposis , cancer research , cell culture , transcription factor , tumor suppressor gene , microbiology and biotechnology , gene , colorectal cancer , carcinogenesis , homeobox , cancer , genetics , sox2
Gut-enriched Krüppel-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 wild-type 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.