Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells

William C. Reinhold; Mark A. Reimers; Alika K. Maunakea; Sohyoung Kim; Samir Lababidi; Uwe Scherf; Uma T. Shankavaram; Micah S. Ziegler; Claudia Stewart; Hosein Kouros-Mehr; Hengmi Cui; Douglas Dolginow; Dominic A. Scudiero; Yves G. Pommier; David J. Munroe; Andrew P. Feinberg; John N. Weinstein

doi:10.1158/1535-7163.MCT-06-0609

Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells

William C. Reinhold, Mark A. Reimers, Alika K. Maunakea, Sohyoung Kim, Samir Lababidi, Uwe Scherf, Uma T. Shankavaram, Micah S. Ziegler, Claudia Stewart, Hosein Kouros-Mehr, Hengmi Cui, Douglas Dolginow, Dominic A. Scudiero, Yves G. Pommier, David J. Munroe, Andrew P. Feinberg, John N. Weinstein

School of Medicine

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

E-cadherin (E-cad) is a adhesion glycoprotein, the expression of which is often reduced in invasive or metastatic tumors. To assess E-cad's distribution among different types of cancer cells, we used bisulfitesequencing for detailed, base-by-base measurement of CpG methylation in E-cad's promoter region in the NCI-60 cell lines. The mean methylation levels of the cell lines were distributed bimodally, with values pushed toward either the high or low end of the methylation scale. The 38 epithelial cell lines showed substantially lower (28%) mean methylation levels compared with the nonepithelial cell lines (58%). The CpG site at -143 with respect to the transcriptional start was commonly methylated at intermediate levels, even in cell lines with low overall DNA methylation. We also profiled the NCI-60 cell lines using Affymetrix U133 microarrays and found E-cad expression to be correlated with E-cad methylation at highly statistically significant levels. Above a threshold of ∼ 20% to 30% mean methylation, the expression of E-cad was effectively silenced. Overall, this study provides a type of detailed analysis of methylation that can also be applied to other cancer-related genes. As has been shown in recent years, DNA methylation status can serve as a biomarker for use in choosing therapy.

Original language	English (US)
Pages (from-to)	391-403
Number of pages	13
Journal	Molecular cancer therapeutics
Volume	6
Issue number	2
DOIs	https://doi.org/10.1158/1535-7163.MCT-06-0609
State	Published - Feb 2007

ASJC Scopus subject areas

Oncology
Cancer Research

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Reinhold, W. C., Reimers, M. A., Maunakea, A. K., Kim, S., Lababidi, S., Scherf, U., Shankavaram, U. T., Ziegler, M. S., Stewart, C., Kouros-Mehr, H., Cui, H., Dolginow, D., Scudiero, D. A., Pommier, Y. G., Munroe, D. J., Feinberg, A. P., & Weinstein, J. N. (2007). Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells. Molecular cancer therapeutics, 6(2), 391-403. https://doi.org/10.1158/1535-7163.MCT-06-0609

Reinhold, WC, Reimers, MA, Maunakea, AK, Kim, S, Lababidi, S, Scherf, U, Shankavaram, UT, Ziegler, MS, Stewart, C, Kouros-Mehr, H, Cui, H, Dolginow, D, Scudiero, DA, Pommier, YG, Munroe, DJ, Feinberg, AP & Weinstein, JN 2007, 'Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells', Molecular cancer therapeutics, vol. 6, no. 2, pp. 391-403. https://doi.org/10.1158/1535-7163.MCT-06-0609

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abstract = "E-cadherin (E-cad) is a adhesion glycoprotein, the expression of which is often reduced in invasive or metastatic tumors. To assess E-cad's distribution among different types of cancer cells, we used bisulfitesequencing for detailed, base-by-base measurement of CpG methylation in E-cad's promoter region in the NCI-60 cell lines. The mean methylation levels of the cell lines were distributed bimodally, with values pushed toward either the high or low end of the methylation scale. The 38 epithelial cell lines showed substantially lower (28%) mean methylation levels compared with the nonepithelial cell lines (58%). The CpG site at -143 with respect to the transcriptional start was commonly methylated at intermediate levels, even in cell lines with low overall DNA methylation. We also profiled the NCI-60 cell lines using Affymetrix U133 microarrays and found E-cad expression to be correlated with E-cad methylation at highly statistically significant levels. Above a threshold of ∼ 20% to 30% mean methylation, the expression of E-cad was effectively silenced. Overall, this study provides a type of detailed analysis of methylation that can also be applied to other cancer-related genes. As has been shown in recent years, DNA methylation status can serve as a biomarker for use in choosing therapy.",

author = "Reinhold, {William C.} and Reimers, {Mark A.} and Maunakea, {Alika K.} and Sohyoung Kim and Samir Lababidi and Uwe Scherf and Shankavaram, {Uma T.} and Ziegler, {Micah S.} and Claudia Stewart and Hosein Kouros-Mehr and Hengmi Cui and Douglas Dolginow and Scudiero, {Dominic A.} and Pommier, {Yves G.} and Munroe, {David J.} and Feinberg, {Andrew P.} and Weinstein, {John N.}",

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AU - Reinhold, William C.

AU - Reimers, Mark A.

AU - Maunakea, Alika K.

AU - Kim, Sohyoung

AU - Lababidi, Samir

AU - Scherf, Uwe

AU - Shankavaram, Uma T.

AU - Ziegler, Micah S.

AU - Stewart, Claudia

AU - Kouros-Mehr, Hosein

AU - Cui, Hengmi

AU - Dolginow, Douglas

AU - Scudiero, Dominic A.

AU - Pommier, Yves G.

AU - Munroe, David J.

AU - Feinberg, Andrew P.

AU - Weinstein, John N.

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N2 - E-cadherin (E-cad) is a adhesion glycoprotein, the expression of which is often reduced in invasive or metastatic tumors. To assess E-cad's distribution among different types of cancer cells, we used bisulfitesequencing for detailed, base-by-base measurement of CpG methylation in E-cad's promoter region in the NCI-60 cell lines. The mean methylation levels of the cell lines were distributed bimodally, with values pushed toward either the high or low end of the methylation scale. The 38 epithelial cell lines showed substantially lower (28%) mean methylation levels compared with the nonepithelial cell lines (58%). The CpG site at -143 with respect to the transcriptional start was commonly methylated at intermediate levels, even in cell lines with low overall DNA methylation. We also profiled the NCI-60 cell lines using Affymetrix U133 microarrays and found E-cad expression to be correlated with E-cad methylation at highly statistically significant levels. Above a threshold of ∼ 20% to 30% mean methylation, the expression of E-cad was effectively silenced. Overall, this study provides a type of detailed analysis of methylation that can also be applied to other cancer-related genes. As has been shown in recent years, DNA methylation status can serve as a biomarker for use in choosing therapy.

AB - E-cadherin (E-cad) is a adhesion glycoprotein, the expression of which is often reduced in invasive or metastatic tumors. To assess E-cad's distribution among different types of cancer cells, we used bisulfitesequencing for detailed, base-by-base measurement of CpG methylation in E-cad's promoter region in the NCI-60 cell lines. The mean methylation levels of the cell lines were distributed bimodally, with values pushed toward either the high or low end of the methylation scale. The 38 epithelial cell lines showed substantially lower (28%) mean methylation levels compared with the nonepithelial cell lines (58%). The CpG site at -143 with respect to the transcriptional start was commonly methylated at intermediate levels, even in cell lines with low overall DNA methylation. We also profiled the NCI-60 cell lines using Affymetrix U133 microarrays and found E-cad expression to be correlated with E-cad methylation at highly statistically significant levels. Above a threshold of ∼ 20% to 30% mean methylation, the expression of E-cad was effectively silenced. Overall, this study provides a type of detailed analysis of methylation that can also be applied to other cancer-related genes. As has been shown in recent years, DNA methylation status can serve as a biomarker for use in choosing therapy.

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Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells

Abstract

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