Clinical Cancer Research The Science of Cancer Health Disparities Infection and Cancer: Biology, Therapeutics, and Prevention
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Corn, P. G.
Right arrow Articles by Herman, J. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Corn, P. G.
Right arrow Articles by Herman, J. G.
Clinical Cancer Research Vol. 6, 4243-4248, November 2000
© 2000 American Association for Cancer Research

Regular Articles

E-Cadherin Expression Is Silenced by 5' CpG Island Methylation in Acute Leukemia1

Paul G. Corn2, B. Douglas Smith, Emily S. Ruckdeschel, Donna Douglas, Stephen B. Baylin and James G. Herman3

The Johns Hopkins Oncology Center, Baltimore, Maryland 21231

ABSTRACT

E-Cadherin is a transmembrane glycoprotein that mediates Ca2+-dependent intercellular adhesion in normal epithelium. In tumors of epithelial origin, E-cadherin expression frequently is reduced, an event that contributes to tumor invasion and metastasis. The role of E-cadherin in hematopoietic tissues is less clear. In normal bone marrow, E-cadherin is expressed on erythroid progenitors, CD34+ stem cells, and stromal cells, where it likely contributes to intercellular interactions during hematopoiesis. In this study, we used a nested-PCR approach to examine the methylation status of the E-cadherin 5' CpG island in blood and bone marrow samples from normal donors and in bone marrow from patients with acute leukemia. In normal peripheral blood mononuclear cells and bone marrow, Ecadherin was completely unmethylated. In peripheral blood mononuclear cells, expression was evident by reverse transcription-PCR. Immunoblotting confirmed E-cadherin protein expression in two lymphoblastoid cell lines derived from normal donors. In contrast, E-cadherin was aberrantly methylated in 4 of 4 (100%) leukemia cell lines, 14 of 44 (32%) acute myelogenous leukemias, and 18 of 33 (53%) acute lymphoblastic leukemias. Genomic bisulfite sequencing of primary leukemias confirmed dense methylation across the CpG island. Methylation was associated with loss of E-cadherin RNA and protein in leukemia cell lines and primary leukemias. Following treatment with 5-aza-2'deoxycytidine, a methylated leukemia cell line expressed both E-cadherin transcript and protein. Our results show that methylation of E-cadherin occurs commonly in acute leukemia and suggests a hypothesis for E-cadherin down-regulation in leukemogenesis.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
E.-S. Lee, J.-P. Issa, D. B. Roberts, M. D. Williams, R. S. Weber, M. S. Kies, and A. K. El-Naggar
Quantitative Promoter Hypermethylation Analysis of Cancer-Related Genes in Salivary Gland Carcinomas: Comparison with Methylation-Specific PCR Technique and Clinical Significance
Clin. Cancer Res., May 1, 2008; 14(9): 2664 - 2672.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Shen, Y. Kondo, S. Ahmed, Y. Boumber, K. Konishi, Y. Guo, X. Chen, J. N. Vilaythong, and J.-P. J. Issa
Drug Sensitivity Prediction by CpG Island Methylation Profile in the NCI-60 Cancer Cell Line Panel
Cancer Res., December 1, 2007; 67(23): 11335 - 11343.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
J. D. Wren, Y. Wu, and S.-W. Guo
A system-wide analysis of differentially expressed genes in ectopic and eutopic endometrium
Hum. Reprod., August 1, 2007; 22(8): 2093 - 2102.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
Y. Wu, A. Starzinski-Powitz, and S.-W. Guo
Trichostatin A, a Histone Deacetylase Inhibitor, Attenuates Invasiveness and Reactivates E-Cadherin Expression in Immortalized Endometriotic Cells
Reproductive Sciences, May 1, 2007; 14(4): 374 - 382.
[Abstract] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
W. C. Reinhold, M. A. Reimers, A. K. Maunakea, S. Kim, S. Lababidi, U. Scherf, U. T. Shankavaram, M. S. Ziegler, C. Stewart, H. Kouros-Mehr, et al.
Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells
Mol. Cancer Ther., February 1, 2007; 6(2): 391 - 403.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. Yuan, J. Wang, J. Li, L. Wang, M. Li, Z. Yang, C. Zhang, and J. L. Dai
Frequent Epigenetic Inactivation of Spleen Tyrosine Kinase Gene in Human Hepatocellular Carcinoma.
Clin. Cancer Res., November 15, 2006; 12(22): 6687 - 6695.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. D. Gore, S. Baylin, E. Sugar, H. Carraway, C. B. Miller, M. Carducci, M. Grever, O. Galm, T. Dauses, J. E. Karp, et al.
Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms.
Cancer Res., June 15, 2006; 66(12): 6361 - 6369.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I. I. de Caceres, C. Battagli, M. Esteller, J. G. Herman, E. Dulaimi, M. I. Edelson, C. Bergman, H. Ehya, B. L. Eisenberg, and P. Cairns
Tumor Cell-Specific BRCA1 and RASSF1A Hypermethylation in Serum, Plasma, and Peritoneal Fluid from Ovarian Cancer Patients
Cancer Res., September 15, 2004; 64(18): 6476 - 6481.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. Dulaimi, I. I. de Caceres, R. G. Uzzo, T. Al-Saleem, R. E. Greenberg, T. J. Polascik, J. S. Babb, W. E. Grizzle, and P. Cairns
Promoter Hypermethylation Profile of Kidney Cancer
Clin. Cancer Res., June 15, 2004; 10(12): 3972 - 3979.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Takahashi, N. Shivapurkar, J. Reddy, H. Shigematsu, K. Miyajima, M. Suzuki, S. Toyooka, S. Zochbauer-Muller, J. Drach, G. Parikh, et al.
DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies
Clin. Cancer Res., May 1, 2004; 10(9): 2928 - 2935.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. Dulaimi, R. G. Uzzo, R. E. Greenberg, T. Al-Saleem, and P. Cairns
Detection of Bladder Cancer in Urine by a Tumor Suppressor Gene Hypermethylation Panel
Clin. Cancer Res., March 15, 2004; 10(6): 1887 - 1893.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. Krassenstein, E. Sauter, E. Dulaimi, C. Battagli, H. Ehya, A. Klein-Szanto, and P. Cairns
Detection of Breast Cancer in Nipple Aspirate Fluid by CpG Island Hypermethylation
Clin. Cancer Res., January 1, 2004; 10(1): 28 - 32.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Battagli, R. G. Uzzo, E. Dulaimi, I. Ibanez de Caceres, R. Krassenstein, T. Al-Saleem, R. E. Greenberg, and P. Cairns
Promoter Hypermethylation of Tumor Suppressor Genes in Urine from Kidney Cancer Patients
Cancer Res., December 15, 2003; 63(24): 8695 - 8699.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. V. Brock, M. Gou, Y. Akiyama, A. Muller, T.-T. Wu, E. Montgomery, M. Deasel, P. Germonpre, L. Rubinson, R. F. Heitmiller, et al.
Prognostic Importance of Promoter Hypermethylation of Multiple Genes in Esophageal Adenocarcinoma
Clin. Cancer Res., August 1, 2003; 9(8): 2912 - 2919.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Jeronimo, I. Costa, M. C. Martins, P. Monteiro, S. Lisboa, C. Palmeira, R. Henrique, M. R. Teixeira, and C. Lopes
Detection of Gene Promoter Hypermethylation in Fine Needle Washings from Breast Lesions
Clin. Cancer Res., August 1, 2003; 9(9): 3413 - 3417.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
P. G. Corn, M. K. Summers, F. Fogt, A. K. Virmani, A. F. Gazdar, T. D. Halazonetis, and W. S. El-Deiry
Frequent hypermethylation of the 5' CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer
Carcinogenesis, January 1, 2003; 24(1): 47 - 51.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
G. Mufti, A. F. List, S. D. Gore, and A. Y.L. Ho
Myelodysplastic Syndrome
Hematology, January 1, 2003; 2003(1): 176 - 199.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Shen, Y. Kondo, J.-P. Issa, G. Garcia-Manero, J. Roman-Gomez, J. A. Castillejo, A. Torres, and A. Jimenez
Lack of p21CIP1 DNA methylation in acute lymphocytic leukemia
Blood, October 16, 2002; 100(9): 3432 - 3433.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. R. Suh, C. S. Ha, E. B. Rankin, M. Toyota, and P. G. Traber
DNA Methylation Down-regulates CDX1 Gene Expression in Colorectal Cancer Cell Lines
J. Biol. Chem., September 20, 2002; 277(39): 35795 - 35800.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
F. J. Giles, A. Keating, A. H. Goldstone, I. Avivi, C. L. Willman, and H. M. Kantarjian
Acute Myeloid Leukemia
Hematology, January 1, 2002; 2002(1): 73 - 110.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
P. Cairns, M. Esteller, J. G. Herman, M. Schoenberg, C. Jeronimo, M. Sanchez-Cespedes, N.-H. Chow, M. Grasso, L. Wu, W. B. Westra, et al.
Molecular Detection of Prostate Cancer in Urine by GSTP1 Hypermethylation
Clin. Cancer Res., September 1, 2001; 7(9): 2727 - 2730.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. G. Corn, E. I. Heath, R. Heitmiller, F. Fogt, A. A. Forastiere, J. G. Herman, and T.-T. Wu
Frequent Hypermethylation of the 5' CpG Island of E-Cadherin in Esophageal Adenocarcinoma
Clin. Cancer Res., September 1, 2001; 7(9): 2765 - 2769.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2000 by the American Association for Cancer Research.