Chfr expression is downregulated by CpG island hypermethylation in esophageal cancer.
Cell cycle progression is monitored by checkpoint mechanisms to ensure the integrity of the genome and the fidelity of sister chromatid separation. Failure of such checkpoint functions results in genomic instability, a condition that predisposes cells to neoplastic transformation and tumor progression. Recently, Scolnick and Halazonetis defined a new mitotic checkpoint that acts at prophase and delays chromosome condensation in response to mitotic stress, and identified a gene, named checkpoint with FHA and ring finger (Chfr), that seems to be required for delaying prophase in human cells. In the present study, we examined human Chfr mRNA expression in 15 human esophageal cancer cell lines and 43 primary esophageal cancers to investigate the potential involvement of Chfr in the pathogenesis of esophageal cancers. We report here that a significant proportion of human esophageal cancer has loss of expression of Chfr gene. Furthermore, we found aberrant hypermethylation of the promoter region of this checkpoint gene in four of 15 (26.7%) esophageal cancer cell lines and in seven of 43 (16.3%) primary cancers.
Shibata
Yasuyuki
Y
Department of Surgery II, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Haruki
Nobuhiro
N
Kuwabara
Yoshiyuki
Y
Ishiguro
Hideyuki
H
Shinoda
Noriyuki
N
Sato
Atsushi
A
Kimura
Masahiro
M
Koyama
Hiroshi
H
Toyama
Tatsuya
T
Nishiwaki
Tadashi
T
Kudo
Junzo
J
Terashita
Yukio
Y
Konishi
Shigeru
S
Sugiura
Hironori
H
Fujii
Yoshitaka
Y
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; D017931:DNA Primers; D015226:Dinucleoside Phosphates; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D044767:Ubiquitin-Protein Ligases; C015772:CpG dinucleotide; C412002:CHFR protein, human