The team investigated the role of gene silencing in human colon cancer, and reported their findings in the latest issue of the Proceedings of the National Academy of Sciences of the United States of America.
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, are disrupted in cancer.
The researchers identified a target for gene inactivation in colon cancer, which was 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 9 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, the authors found that HLTF methylation was detected in 27 of 63 cases (43%).
| Methylation of HLTF detected in 40% of colon carcinomas.
No methylation of HLTF was detected in breast or lung cancers. This suggested selection for HLTF methylation in colonic malignancies.
Transfection of HLTF suppressed 75% of colony growth in each of 3 different HLTF-deficient cell lines.
However, this showed no suppressive effect in any of 3 HLTF-proficient cell lines.
Helen R. Moinova, of the Case Western Reserve University, Cleveland, Ohio, concluded on behalf of her colleagues, "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."