Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-11-6
pubmed:abstractText
Cancer cells differ from normal cells in many aspects, including hyperproliferation and loss of differentiation. Recent research has focused on the role of transcription factors in regulating abnormal cell growth. Gut-enriched Krüppel-like factor (GKLF) is a newly identified eukaryotic zinc finger protein expressed extensively in the gastrointestinal tract. In the current study, we demonstrated that GKLF mRNA levels were significantly decreased in the dysplastic epithelium of the colon, including adenomatous polyp and cancer. GKLF immunostains in the normal colon were higher at the surface epithelium and gradually decreased toward the crypt, but this gradient was not present in the adenomatous and cancerous mucosa. Constitutive overexpression of GKLF DNA in a human colonic adenocarcinoma cell line (HT-29) decreased [(3)H]thymidine incorporation, whereas suppression of GKLF gene increased DNA synthesis, indicating that downregulation of the GKLF gene might contribute to cellular hyperproliferation. Cyclin D1 (CD1) protein level and CD1-associated kinase activity were decreased in HT-29 cell overexpressed GKLF cDNA, and CD1 promoter activity was profoundly suppressed by GKLF. When HT-29 cells were cultured in the presence of sodium butyrate, GKLF mRNA levels increased as cells acquired more differentiated phenotypes. These results suggest that GKLF plays an important role in regulating cell growth and differentiation in the colonic epithelium and that downregulation of GKLF expression may cause colonic cells to become hyperproliferative. Furthermore, GKLF appears to be a transcriptional repressor of the CD1 gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G806-14
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11005769-Adenomatous Polyposis Coli, pubmed-meshheading:11005769-Antibodies, pubmed-meshheading:11005769-Cell Differentiation, pubmed-meshheading:11005769-Cell Division, pubmed-meshheading:11005769-Colon, pubmed-meshheading:11005769-Colonic Neoplasms, pubmed-meshheading:11005769-DNA-Binding Proteins, pubmed-meshheading:11005769-Growth Inhibitors, pubmed-meshheading:11005769-Humans, pubmed-meshheading:11005769-Kruppel-Like Transcription Factors, pubmed-meshheading:11005769-RNA, Messenger, pubmed-meshheading:11005769-Recombinant Fusion Proteins, pubmed-meshheading:11005769-Recombinant Proteins, pubmed-meshheading:11005769-Transcription, Genetic, pubmed-meshheading:11005769-Transcription Factors, pubmed-meshheading:11005769-Transfection, pubmed-meshheading:11005769-Tumor Cells, Cultured, pubmed-meshheading:11005769-Zinc Fingers
pubmed:year
2000
pubmed:articleTitle
Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.
pubmed:affiliation
Section of Gastroenterology, Boston Veterans Affairs Medical Center and Boston University School of Medicine, Boston, Massachusetts 02118, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't