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Research Paper
Epigenetic Inactivation of EGFR by CpG Island Hypermethylation in Cancer
Alberto J. Montero, C. Marcela Díaz-Montero, Li Mao, Emile Youssef, Marcos Estecio, Lanlan Shen and Jean-Pierre J. Issa
volume 5 | issue 11
November 2006Pages: 1494 - 1501
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The epidermal growth factor receptor (EGFR) is a member of the HER/ERB-B family of transmembrane receptor kinases. Overexpression of EGFR confers advantages in cell proliferation, survival, and migration and correlates with decreased survival in multiple solid tumors. However, a proportion of these malignancies have little or no expression of EGFR. CpG island hypermethylation and associated transcriptional silencing are common in solid tumors. The methylation status of the EGFR CpG island was examined in a series of cell lines and tissues. Dense EGFR methylation (90%) was found in the breast cancer cell line CAMA1, and a moderate degree of methylation (30-50%) was observed in the breast cancer cell lines MB435 and MB453. Transcriptional silencing of EGFR in these cell lines closely correlated with methylation. By contrast, no methylation of the HER-2/neu CpG island was detected. EGFR hypermethylation was also found in a subset of unselected primary breast (20%), head and neck squamous cell carcinoma (35%), and lung tumors (11%). Treatment with decitabine resulted in the reexpression of EGFR in CAMA1 and MB453. Both cell lines are relatively resistant to killing by the EGFR inhibitor gefitinib. However, after co-treatment with decitabine and gefitinib, a significant effect on the induction of apoptosis was observed. In conclusion, EGFR is hypermethylated and silenced in a subset of solid tumor cell lines and primary tumor specimens, and co-treatment with decitabine and gefitinib has an additive effect only in EGFR methylated breast cancer cell lines.
Authors
Alberto J. Montero
University of South Carolina, Charleston, SC
C. Marcela Díaz-Montero
University of South Carolina, Charleston, SC
Li Mao
Anderson Cancer Center, Houston, TX
Emile Youssef
Novartis Pharma
Marcos Estecio
Anderson Cancer Center, Houston, TX
Lanlan Shen
Anderson Cancer Center, Houston, TX
Jean-Pierre J. Issa
Anderson Cancer Center, Houston, TX
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.