期刊
ONCOGENE
卷 20, 期 35, 页码 4884-4890出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204645
关键词
gut-enriched Kruppel-like factor; Kruppel-like factor 4; colon cancer; CDX2; adenomatous polyposis coli; dominant negative
资金
- 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
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据