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Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer.

Publication ,  Journal Article
Wang, W; Huper, G; Guo, Y; Murphy, SK; Olson, JA; Marks, JR
Published in: Oncogene
April 14, 2005

Treatment of the breast cancer cell line, MDAMB468 with the DNA methylation inhibitor, 5-azacytidine (5-AzaC) results in growth arrest, whereas the growth of the normal breast epithelial line DU99 (telomerase immortalized) is relatively unaffected. Comparing gene expression profiles of these two lines after 5-AzaC treatment, we identified 36 genes that had relatively low basal levels in MDAMB468 cells compared to the DU99 line and were induced in the cancer cell line but not in the normal breast epithelial line. Of these genes, 33 have associated CpG islands greater than 300 bp in length but only three have been previously described as targets for aberrant methylation in human cancer. Northern blotting for five of these genes (alpha-Catenin, DTR, FYN, GADD45a, and Zyxin) verified the array results. Further analysis of one of these genes, GADD45a, showed that 5-AzaC induced expression in five additional breast cancer cell lines with little or no induction in three additional lines derived from normal breast epithelial cells. The CpG island associated with GADD45a was analysed by bisulfite sequencing, sampling over 100 CpG dinucleotides. We found that four CpG's, located approximately 700 bp upstream of the transcriptional start site are methylated in the majority of breast cancer cell lines and primary tumors but not in DNA from normal breast epithelia or matched lymphocytes from cancer patients. Therefore, this simple method of dynamic transcriptional profiling yielded a series of novel methylation-sensitive genes in breast cancer including the BRCA1 and p53 responsive gene, GADD45a.

Duke Scholars

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

April 14, 2005

Volume

24

Issue

16

Start / End Page

2705 / 2714

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Proteins
  • Molecular Sequence Data
  • Humans
  • Gene Expression Profiling
  • Female
  • Epithelial Cells
  • DNA Methylation
 

Citation

APA
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ICMJE
MLA
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Wang, W., Huper, G., Guo, Y., Murphy, S. K., Olson, J. A., & Marks, J. R. (2005). Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer. Oncogene, 24(16), 2705–2714. https://doi.org/10.1038/sj.onc.1208464
Wang, Wei, Gudrun Huper, Yueqi Guo, Susan K. Murphy, John A. Olson, and Jeffrey R. Marks. “Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer.Oncogene 24, no. 16 (April 14, 2005): 2705–14. https://doi.org/10.1038/sj.onc.1208464.
Wang W, Huper G, Guo Y, Murphy SK, Olson JA, Marks JR. Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer. Oncogene. 2005 Apr 14;24(16):2705–14.
Wang, Wei, et al. “Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer.Oncogene, vol. 24, no. 16, Apr. 2005, pp. 2705–14. Pubmed, doi:10.1038/sj.onc.1208464.
Wang W, Huper G, Guo Y, Murphy SK, Olson JA, Marks JR. Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer. Oncogene. 2005 Apr 14;24(16):2705–2714.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

April 14, 2005

Volume

24

Issue

16

Start / End Page

2705 / 2714

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Proteins
  • Molecular Sequence Data
  • Humans
  • Gene Expression Profiling
  • Female
  • Epithelial Cells
  • DNA Methylation