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PMID: 14724568 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.

Oncogene ·Vol. 23 ·No. 2 ·2004-01-15 ·Pages 395-402

Zhao W, Hisamuddin IM, Nandan MO, Babbin BA, Lamb NE, Yang VW

Abstract

Krüppel-like factor 4 (KLF4 or GKLF) is an inhibitor of the cell cycle. The gene encoding KLF4 is localized on chromosome 9q, previously shown to exhibit allelic loss in colorectal cancer (CRC). In this study, we show that the mean level of KLF4 mRNA in a panel of 30 CRC was 52% that of paired normal colonic tissues. Similarly, the levels of KLF4 mRNA and protein in a panel of six established CRC cell lines were significantly lower than those of an untransformed colonic epithelial cell line. Using highly polymorphic DNA markers that flank the KLF4 locus, we found evidence for loss of heterozygosity (LOH) in two of eight surgically resected CRC specimens. In addition, LOH was observed in five of six CRC cell lines with one additional cell line exhibiting hemizygous deletion in the KLF4 gene. We also found that the 5'-untranslated region of KLF4 was hypermethylated in a subset of resected CRC specimens and cell lines. Lastly, the open-reading frame of KLF4 in two of three CRC cell lines examined contained several point mutations that resulted in a diminished ability to activate the p21(WAF1/Cip1) promoter. These findings indicate that KLF4 is a potential tumor suppressor gene in CRC.

MeSH Terms
5' Untranslated Regions/genetics Amino Acid Sequence Base Sequence Blotting, Southern Blotting, Western Cell Line, Tumor Colonic Neoplasms/genetics Colorectal Neoplasms/genetics DNA Methylation DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor/physiology Humans Kruppel-Like Factor 4 Kruppel-Like Transcription Factors Loss of Heterozygosity/genetics Molecular Sequence Data Point Mutation/genetics RNA, Messenger/genetics,metabolism Transcription Factors/genetics,metabolism
Chemicals
5' Untranslated Regions DNA-Binding Proteins KLF4 protein, human Kruppel-Like Factor 4 Kruppel-Like Transcription Factors RNA, Messenger Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhao Weidong
Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
Hisamuddin Irfan M
Nandan Mandayam O
Babbin Brian A
Lamb Neil E
Yang Vincent W
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Article Info
Journal
Oncogene
Abbr.
Oncogene
ISSN
0950-9232
DOI
10.1038/sj.onc.1207067
Published
2004-01-15
Pages
395-402
Language
English
Region
England
NLM ID
8711562
PMCID
PMC1351029
Subset
IM
Grants
NIDDK NIH HHS · R01 DK052230 · United States
NIDDK NIH HHS · DK64399 · United States
NCI NIH HHS · R01 CA084197 · United States
NIDDK NIH HHS · R24 DK064399 · United States
NIDDK NIH HHS · DK52230 · United States
NCI NIH HHS · CA84197 · United States
External Links
PubMed source DOI: 10.1038/sj.onc.1207067 PMC Full Text View journal details
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