title: HLTF gene silencing in human colon cancer.
abstract: 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.
authors.affiliation: Cancer Center and Department of Medicine at Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Moinova
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
authors.forename: Lanlan
authors.initials: L
authors.lastname: Shen
authors.forename: Dominic
authors.initials: D
authors.lastname: Smiraglia
authors.forename: Joseph
authors.initials: J
authors.lastname: Olechnowicz
authors.forename: Lakshmeswari
authors.initials: L
authors.lastname: Ravi
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Kasturi
authors.forename: Lois
authors.initials: L
authors.lastname: Myeroff
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Ramon
authors.initials: R
authors.lastname: Parsons
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.forename: Sylvan B
authors.initials: SB
authors.lastname: Green
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Issa
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D014157:Transcription Factors