Epigenetic Silencing of Cell Adhesion Molecule 1 in Different Cancer Progenitor Cells of Transgenic c-Myc and c-Raf Mouse Lung Tumors

Reamon-Buettner, Stella Marie; Borlak, Jürgen

doi:10.1158/0008-5472.can-08-0967

Cited by 26 publications

(26 citation statements)

References 35 publications

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“…A wide range of concentrations of mithramycin A (10 nM - 1 μM) have been used to inhibit the transcriptional activity of Sp1 in various types of cells, including human bronchial epithelial cells and multiple myeloma cells [17,18]. Data from the present study showed that mithramycin A did not alter the Sp1 protein level (Fig.…”

Section: Resultsmentioning

confidence: 58%

Overexpression of antioxidant enzymes upregulates aryl hydrocarbon receptor expression via increased Sp1 DNA-binding activity

Tang

Lin

Hong

et al. 2010

Free Radical Biology and Medicine

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We previously reported up-regulation of aryl hydrocarbon receptor (AhR) expression as a mechanism by which overexpression of Cu/Zn-superoxide dismutase (SOD) and/or catalase accelerates benzo(a)pyrene (BaP) detoxification in mouse aorta endothelial cells (MAECs). The objective of this study was to investigate the regulatory role of specificity protein-1 (Sp1) in AhR expression in MAECs that overexpress Cu/Zn-SOD and/or catalase. Our data demonstrated comparable levels of nuclear Sp1 protein in the transgenic and wild-type MAECs; however, binding of Sp1 protein to the AhR promoter region was more than 2-fold higher in MAECs overexpressing Cu/Zn-SOD and/or catalase than in wild-type cells. Inhibition of Sp1 binding to the AhR promoter by mithramycin A reduced AhR expression and eliminated the differences between wild-type MAECs, and three lines of transgenic cells. Functional promoter analysis indicated that AhR promoter activity was significantly higher in MAECs overexpressing catalase than in wild-type cells. Mutation of an AhR promoter Sp1-binding site or addition of hydrogen peroxide to the culture medium reduced AhR promoter activity, and decreased the differences between wild-type MAECs and transgenic cells overexpressing catalase. These results suggest that increased Sp1 binding to the AhR promoter region is an underlying mechanism for up-regulation of AhR expression in MAECs that overexpress Cu/Zn-SOD and/or catalase.

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Section: Resultsmentioning

confidence: 58%

Overexpression of antioxidant enzymes upregulates aryl hydrocarbon receptor expression via increased Sp1 DNA-binding activity

Tang

Lin

Hong

et al. 2010

Free Radical Biology and Medicine

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“…The binding of SP1 to target genes can be interrupted by DNA methylation, resulting in the silencing of gene expression. A number of genes with GC-rich promoter regions, such as CADM1 (24), KEAP1 (25), and NDRG2 (26), were found to be regulated by the combined effects of SP1 and DNA methylation. In this study, we identified FOXF2 as a novel transcriptional target of SP1 and demonstrated that the CpG island methylation of the FOXF2 proximal promoter region abrogated SP1 binding, leading to the silencing of FOXF2 expression.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

Tian

Lun

Huang

et al. 2015

Journal of Biological Chemistry

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Background: Promoter hypermethylation affects the regulation of transcription factors for target genes. Results: SP1 activates FOXF2 transcription, but this activation is prevented through FOXF2 promoter methylation. Conclusion: FOXF2 transcription is regulated through the combined effects of DNA methylation and SP1 transcriptional regulation. Significance: Herein, we describe a new regulatory mechanism for the subtype-specific expression of FOXF2 in breast cancer.

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“…Notably, the transgenic cell lines display epigenetic plasticity and express several tumor stem cell markers providing a mechanistic insight into lung cancer as recently reported by us. 16 The murine cell lines were more resistant, with IC 50 values typically in the region of 1 lM. A comparison between the compounds that include one unit of camptothecin (10-12) and the ones with two units (6-8), evidenced for these latter a higher antiproliferative activity.…”

Section: Antiproliferative Activitymentioning

confidence: 97%

Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20

Riva¹,

Comi²,

Borrelli³

et al. 2010

Bioorganic & Medicinal Chemistry

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Epigenetic Silencing of Cell Adhesion Molecule 1 in Different Cancer Progenitor Cells of Transgenic c-Myc and c-Raf Mouse Lung Tumors

Abstract: Understanding molecular mechanisms underlying lung cancer is a prerequisite toward treatment.

Cited by 26 publications

References 35 publications

Overexpression of antioxidant enzymes upregulates aryl hydrocarbon receptor expression via increased Sp1 DNA-binding activity

Overexpression of antioxidant enzymes upregulates aryl hydrocarbon receptor expression via increased Sp1 DNA-binding activity

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20

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