Decreased expression of the gut-enriched Krüppel-like factor gene in intestinal adenomas of multiple intestinal neoplasia mice and in colonic adenomas of familial adenomatous polyposis patients.
Gut-enriched Krüppel-like factor (GKLF) is a zinc finger-containing transcription factor, the expression of which is associated with growth arrest. We compared Gklf expression in intestinal and colonic adenomas to normal mucosa in multiple intestinal neoplasia (Min) mice and familial adenomatous polyposis (FAP) patients, respectively, using semi-quantitative RT-PCR. In Min mice, the level of Gklf transcript is highest in normal-appearing intestinal tissues and decreases as the size of the adenoma increases. In FAP patients, the level of GKLF transcript is lower in adenomas compared to paired normal-appearing mucosa from the same patient or normal colonic mucosa from control individuals without FAP. The possibility of DNA methylation as a cause for the decreased expression of Gklf in adenomas of Min mice was investigated by methylation-specific PCR. Results indicate that the Gklf gene is not methylated in either normal or tumorous tissues. The findings of our study are therefore consistent with the potential role of GKLF as a negative growth regulator of gut epithelial cells.
Dang
D T
DT
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Bachman
K E
KE
Mahatan
C S
CS
Dang
L H
LH
Giardiello
F M
FM
Yang
V W
VW
D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D006131:Growth Inhibitors / Q000235:genetics*; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors