HLTF gene silencing in human colon cancer

Helen R. Moinova, Wei Dong Chen, Lanlan Shen, Dominic Smiraglia, Joseph Olechnowicz, Lakshmeswari Ravi, Lakshmi Kasturi, Lois Myeroff, Christoph Plass, Ramon Parsons, John Minna, James K V Willson, Sylvan B. Green, Jean Pierre Issa, Sanford D. Markowitz

Research output: Contribution to journalArticle

128 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4562-4567
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number7
DOIs
StatePublished - Apr 2 2002

Keywords

  • Methylation
  • SWI/SNF

ASJC Scopus subject areas

  • General

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    Moinova, H. R., Chen, W. D., Shen, L., Smiraglia, D., Olechnowicz, J., Ravi, L., Kasturi, L., Myeroff, L., Plass, C., Parsons, R., Minna, J., Willson, J. K. V., Green, S. B., Issa, J. P., & Markowitz, S. D. (2002). HLTF gene silencing in human colon cancer. Proceedings of the National Academy of Sciences of the United States of America, 99(7), 4562-4567. https://doi.org/10.1073/pnas.062459899