Inhibition of DNA methyltransferase stimulates the expression of signal transducer and activator of transcription 1, 2, and 3 genes in colon tumor cells

Adam R Karpf, Peter W. Peterson, Joseph T. Rawlins, Brian K. Dalley, Qian Yang, Hans Albertsen, David A. Jones

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Abstract

Inhibitors of DNA methyltransferase, typified by 5-aza-2'-deoxycytidine (5-Aza-CdR), induce the expression of genes transcriptionally down-regulated by de novo methylation in tumor cells. We utilized gene expression microarrays to examine the effects of 5-Aza-CdR treatment in HT29 colon adenocarcinoma cells. This analysis revealed the induction of a set of genes that implicated IFN signaling in the HT29 cellular response to 5-Aza-CdR. Subsequent investigations revealed that the induction of this gene set correlates with the induction of signal transducer and activator of transcription (STAT) 1, 2, and 3 genes and their activation by endogenous IFN-α. These observations implicate the induction of the IFN-response pathway as a major cellular response to 5-Aza-CdR and suggests that the expression of STATs 1, 2, and 3 can be regulated by DNA methylation. Consistent with STAT's limiting cell responsiveness to IFN, we found that 5- Aza-CdR treatment sensitized HT29 cells to growth inhibition by exogenous IFN-α2a, indicating that 5-Aza-CdR should be investigated as a potentiator of IFN responsiveness in certain IFN-resistant tumors.

Original languageEnglish (US)
Pages (from-to)14007-14012
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number24
DOIs
StatePublished - Nov 23 1999

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STAT2 Transcription Factor
STAT1 Transcription Factor
STAT3 Transcription Factor
Methyltransferases
Colon
decitabine
DNA
Genes
Gene Expression
Neoplasms
HT29 Cells
DNA Methylation
Methylation
Transcriptional Activation
Adenocarcinoma
Growth

ASJC Scopus subject areas

  • General

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Inhibition of DNA methyltransferase stimulates the expression of signal transducer and activator of transcription 1, 2, and 3 genes in colon tumor cells. / Karpf, Adam R; Peterson, Peter W.; Rawlins, Joseph T.; Dalley, Brian K.; Yang, Qian; Albertsen, Hans; Jones, David A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 24, 23.11.1999, p. 14007-14012.

Research output: Contribution to journalArticle

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AU - Jones, David A.

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