This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiraguri, S. Articles by Gray, J. Search for Related Content PubMed PubMed Citation Articles by Hiraguri, S. Articles by Gray, J.

Mechanisms of Inactivation of E-Cadherin in Breast Cancer Cell Lines¹

University of California San Francisco Cancer Center, University of California, San Francisco, California 94143-0808 [S. H., T. G., H. N., L. S., D. P., J. G.]; Johns Hopkins University Oncology Center, Baltimore, Maryland 21231 [J. G., J. H., S. B.]; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 [C. C.]; Los Alamos National Laboratory, Los Alamos, New Mexico 87545 [N. D.]; and University of Toledo, Toledo, Ohio 43606 [K. J., M. W.]

Loss of E-cadherin (CDH1) function is thought to contribute to progression in breast cancer and other solid tumors by increasing proliferation, invasion, and/or metastasis. In some cases, the restoration of CDH1 function may be an important therapeutic option. This possibility will depend on the mechanism by which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic mutation, and promoter methylation in CDH1 in 10 commonly used breast cancer cell lines. Five cell lines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D) expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB-134 IV, CAMA1, and MDA-MB-435) did not express CDH1. Fluorescence in situ hybridization analyses of each of these cell lines showed evidence for the physical deletion of one allele of CDH1, and three cell lines were found to carry homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon 6 was deleted in MDA-MB-134 IV cells, and 600 MPE cells carried a 21-bp deletion in the splicing acceptor site for exon 9. CAMA1 seemed to have been inactivated through promoter methylation. No explanation was found for the inactivation of CDH1 in MDA-MB-435.

¹ Supported by USPHS Grant CA58207, United States Department of Energy Contract DE-AC-03-76SF00098, and Vysis, Inc.

² To whom requests for reprints should be addressed, at Cancer Genetics Program, University of California San Francisco Cancer Center, University of California, San Francisco, CA 94143-0808. Phone: (415) 476-3461; Fax: (415) 476-8218; E-mail: gray@cc.ucsf.edu.

Received 5/19/97. Accepted 3/ 4/98.

This article has been cited by other articles:

				A. Dhasarathy, M. Kajita, and P. A. Wade The Transcription Factor Snail Mediates Epithelial to Mesenchymal Transitions by Repression of Estrogen Receptor-{alpha} Mol. Endocrinol., December 1, 2007; 21(12): 2907 - 2918. [Abstract] [Full Text] [PDF]

				A. P. Vamvakidou, M. J. Mondrinos, S. P. Petushi, F. U. Garcia, P. I. Lelkes, and A. Tozeren Heterogeneous Breast Tumoroids: An In Vitro Assay for Investigating Cellular Heterogeneity and Drug Delivery J Biomol Screen, February 1, 2007; 12(1): 13 - 20. [Abstract] [PDF]

				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]

				J. S. Reis-Filho, P. T. Simpson, N. C. Turner, M. B. Lambros, C. Jones, A. Mackay, A. Grigoriadis, D. Sarrio, K. Savage, T. Dexter, et al. FGFR1 Emerges as a Potential Therapeutic Target for Lobular Breast Carcinomas. Clin. Cancer Res., November 15, 2006; 12(22): 6652 - 6662. [Abstract] [Full Text] [PDF]

				H. Nakamura, I. Aute, N. Kawasaki, M. Taguchi, T. Ohira, and H. Kato Quantitative Detection of Lung Cancer Cells by Fluorescence In Situ Hybridization: Comparison With Conventional Cytology Chest, August 1, 2005; 128(2): 906 - 911. [Abstract] [Full Text] [PDF]

				H. Huang, J. Groth, K. Sossey-Alaoui, L. Hawthorn, S. Beall, and J. Geradts Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors Clin. Cancer Res., June 15, 2005; 11(12): 4357 - 4364. [Abstract] [Full Text] [PDF]

				A. A. Melnikov, R. B. Gartenhaus, A. S. Levenson, N. A. Motchoulskaia, and V. V. Levenson (Chernokhvostov) MSRE-PCR for analysis of gene-specific DNA methylation Nucleic Acids Res., June 8, 2005; 33(10): e93 - e93. [Abstract] [Full Text] [PDF]

				W. Fan, X. Huang, C. Chen, J. Gray, and T. Huang TBX3 and Its Isoform TBX3+2a Are Functionally Distinctive in Inhibition of Senescence and Are Overexpressed in a Subset of Breast Cancer Cell Lines Cancer Res., August 1, 2004; 64(15): 5132 - 5139. [Abstract] [Full Text] [PDF]

				K. O. Toyooka, S. Toyooka, A. Maitra, Q. Feng, N. C. Kiviat, A. Smith, J. D. Minna, R. Ashfaq, and A. F. Gazdar Establishment and Validation of Real-Time Polymerase Chain Reaction Method for CDH1 Promoter Methylation Am. J. Pathol., August 1, 2002; 161(2): 629 - 634. [Abstract] [Full Text] [PDF]

				T. Saito, Y. Oda, K. Sugimachi, K.-i. Kawaguchi, S. Tamiya, K. Tanaka, S. Matsuda, A. Sakamoto, Y. Iwamoto, and M. Tsuneyoshi E-Cadherin Gene Mutations Frequently Occur in Synovial Sarcoma as a Determinant of Histological Features Am. J. Pathol., December 1, 2001; 159(6): 2117 - 2124. [Abstract] [Full Text] [PDF]

				J M D Wheeler, H C Kim, J A Efstathiou, M Ilyas, N J M. Mortensen, and W F Bodmer Hypermethylation of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer Gut, March 1, 2001; 48(3): 367 - 371. [Abstract] [Full Text] [PDF]

				J. E. De Larco, B. R. K. Wuertz, K. A. Rosner, S. A. Erickson, D. E. Gamache, J. C. Manivel, and L. T. Furcht A Potential Role for Interleukin-8 in the Metastatic Phenotype of Breast Carcinoma Cells Am. J. Pathol., February 1, 2001; 158(2): 639 - 646. [Abstract] [Full Text] [PDF]

				M. van de Wetering, N. Barker, I. C. Harkes, M. van der Heyden, N. J. Dijk, A. Hollestelle, J. G. M. Klijn, H. Clevers, and M. Schutte Mutant E-cadherin Breast Cancer Cells Do Not Display Constitutive Wnt Signaling Cancer Res., January 1, 2001; 61(1): 278 - 284. [Abstract] [Full Text]

				T. Yoshida, H. Eguchi, K. Nakachi, K. Tanimoto, Y. Higashi, K. Suemasu, Y. Iino, Y. Morishita, and S.-i. Hayashi Distinct mechanisms of loss of estrogen receptor {{alpha}} gene expression in human breast cancer: methylation of the gene and alteration of trans-acting factors Carcinogenesis, December 1, 2000; 21(12): 2193 - 2201. [Abstract] [Full Text] [PDF]

				H C Kim, J M D Wheeler, J C Kim, M Ilyas, N E Beck, B S Kim, K C Park, and W F Bodmer The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea Gut, August 1, 2000; 47(2): 262 - 267. [Abstract] [Full Text] [PDF]

				S. J. Nass, J. G. Herman, E. Gabrielson, P. W. Iversen, F. F. Parl, N. E. Davidson, and J. R. Graff Aberrant Methylation of the Estrogen Receptor and E-Cadherin 5' CpG Islands Increases with Malignant Progression in Human Breast Cancer Cancer Res., August 1, 2000; 60(16): 4346 - 4348. [Abstract] [Full Text]

				Y. Ohene-Abuakwa and M. Pignatelli Adhesion Molecules as Diagnostic Tools in Tumor Pathology International Journal of Surgical Pathology, July 1, 2000; 8(3): 191 - 200. [Abstract] [PDF]

				J. R. Melki, P. C. Vincent, R. D. Brown, and S. J. Clark Hypermethylation of E-cadherin in leukemia Blood, May 15, 2000; 95(10): 3208 - 3213. [Abstract] [Full Text] [PDF]

				F. Moinfar, Y. G. Man, L. Arnould, G. L. Bratthauer, M. Ratschek, and F. A. Tavassoli Concurrent and Independent Genetic Alterations in the Stromal and Epithelial Cells of Mammary Carcinoma: Implications for Tumorigenesis Cancer Res., May 1, 2000; 60(9): 2562 - 2566. [Abstract] [Full Text]

				S. Hosono, I. Gross, M. A. English, K. M. Hajra, E. R. Fearon, and J. D. Licht E-cadherin Is a WT1 Target Gene J. Biol. Chem., April 6, 2000; 275(15): 10943 - 10953. [Abstract] [Full Text] [PDF]

				M von Schlippe, J. Marshall, P Perry, M Stone, A. Zhu, and I. Hart Functional interaction between E-cadherin and alphav-containing integrins in carcinoma cells J. Cell Sci., January 2, 2000; 113(3): 425 - 437. [Abstract] [PDF]

				K.-F. Becker, E. Kremmer, M. Eulitz, I. Becker, G. Handschuh, C. Schuhmacher, W. Muller, H. E. Gabbert, A. Ochiai, S. Hirohashi, et al. Analysis of E-Cadherin in Diffuse-Type Gastric Cancer Using a Mutation-Specific Monoclonal Antibody Am. J. Pathol., December 1, 1999; 155(6): 1803 - 1809. [Abstract] [Full Text] [PDF]