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Background

Glutathione S-transferases M2 (GST-M2) is a detoxifying enzyme. Low expression levels of GST-M2 have been detected in lung cancer cells. However, little is known about the regulation of GST-M2 in lung cancer cells. In this study, the authors investigated the epigenetic regulatory mechanisms of GST-M2 in lung cancer cells.

Methods

The authors evaluated the promoter methylation of GST-M2 in lung cancer cells after treatment with the DNA methyltransferase (DNMT) inhibitor 5'-aza-2'-deoxycytidine (5'-aza-dC). Reporter activity assays, chromatin immunoprecipitation (ChIP), electrophoretic mobility-shift assays, and small interfering RNA (siRNA) assays were used to determine whether the methylation of specificity protein 1 (Sp1) affected binding to the GST-M2 promoter or regulated GST-M2 transcription. Real-time polymerase chain reaction was used to determine GST-M2 and DNMT-3b messenger RNA levels in 73 nonsmall cell lung cancer (NSCLC) tissues.

Results

GST-M2 expression was restored after treatment with 5'-aza-dC in lung cancer cells. GST-M2 exhibited high frequency of promoter hypermethylation in lung cancer cells and NSCLC tumor tissues. CpG hypermethylation abated Sp1 binding to the GST-M2 promoter in lung cancer. Knockdown of Sp1 in normal lung cells reduced GST-M2 expression, and silencing of DNMT-3b increased GST-M2 expression in lung cancer cells. In addition, DNMT-3b expression was significantly higher in lung tumors with low levels of GST-M2 expression than in lung tumors with high levels of GST-M2 expression, especially among women and among patients who had stage I disease.

Conclusions

Epigenetic silencing of GST-M2 was distinguished from Sp1-mediated GST-M2 transcriptional expression. The authors concluded that this represents a mechanism that leads to decreased expression of GST-M2 in lung cancer cells."xsd:string
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http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/author"Lai C.H."xsd:string
http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/author"Liu Y.F."xsd:string
http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/author"Hsu C.P."xsd:string
http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/author"Wu M.F."xsd:string
http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/author"Ko J.L."xsd:string
http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/author"Tang S.C."xsd:string
http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/author"Wong R.H."xsd:string
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http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/title"Epigenetic mechanisms for silencing glutathione S-transferase m2 expression by hypermethylated specificity protein 1 binding in lung cancer."xsd:string
http://purl.uniprot.org/citations/21246532http://purl.uniprot.org/core/volume"117"xsd:string
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