HLTF gene silencing in human colon cancer.
Chromatin remodeling enzymes are increasingly implicated in a variety of important cellular functions. Various components of chromatin remodeling complexes, including several members of the SWI/SNF family, have been shown to be disrupted in cancer. In this study we identified as a target for gene inactivation in colon cancer the gene for helicase-like transcription factor (HLTF), a SWI/SNF family protein. Loss of HLTF expression accompanied by HLTF promoter methylation was noted in nine of 34 colon cancer cell lines. In these cell lines HLTF expression was restored by treatment with the demethylating agent 5-azacytidine. In further studies of primary colon cancer tissues, HLTF methylation was detected in 27 of 63 cases (43%). No methylation of HLTF was detected in breast or lung cancers, suggesting selection for HLTF methylation in colonic malignancies. Transfection of HLTF suppressed 75% of colony growth in each of three different HLTF-deficient cell lines, but showed no suppressive effect in any of three HLTF-proficient cell lines. These findings show that HLTF is a common target for methylation and epigenetic gene silencing in colon cancer and suggest HLTF is a candidate colon cancer suppressor gene.
Moinova
Helen R
HR
Cancer Center and Department of Medicine at Case Western Reserve University, Cleveland, OH 44106, USA.
Chen
Wei-Dong
WD
Shen
Lanlan
L
Smiraglia
Dominic
D
Olechnowicz
Joseph
J
Ravi
Lakshmeswari
L
Kasturi
Lakshmi
L
Myeroff
Lois
L
Plass
Christoph
C
Parsons
Ramon
R
Minna
John
J
Willson
James K V
JK
Green
Sylvan B
SB
Issa
Jean-Pierre
JP
Markowitz
Sanford D
SD
D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D014157:Transcription Factors