Mechanisms of inactivation of E-cadherin in breast cancer cell lines

Shunsuke Hiraguri, Tony Godfrey, Haruhiko Nakamura, Jeremy Graff, Collin Collins, Laleh Shayesteh, Norman Doggett, Keith Johnson, Margaret Wheelock, James Herman, Stephen Baylin, Daniel Pinkel, Joe Gray

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1972-1977
Number of pages6
JournalCancer Research
Volume58
Issue number9
StatePublished - May 1 1998

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hiraguri, S., Godfrey, T., Nakamura, H., Graff, J., Collins, C., Shayesteh, L., Doggett, N., Johnson, K., Wheelock, M., Herman, J., Baylin, S., Pinkel, D., & Gray, J. (1998). Mechanisms of inactivation of E-cadherin in breast cancer cell lines. Cancer Research, 58(9), 1972-1977.