|Oesterreich, Steffi - BAYLOR COLLEGE MED|
|Deng, Wanleng - BAYLOR COLLEGE MED|
|Jiang, Shiming - BAYLOR COLLEGE MED|
|Cui, Xiaojiang - BAYLOR COLLEGE MED|
|Ivanova, Margarita - BAYLOR COLLEGE MED|
|Schiff, Rachel - BAYLOR COLLEGE MED|
|Kang, Kaiyan - BAYLOR COLLEGE MED|
|Behrens, Jurgen - FRIEDRICH-ALEXANDER UNIV|
|Lee, Adrian - BAYLOR COLLEGE MED|
Submitted to: Cancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 17, 2003
Publication Date: September 1, 2003
Citation: Oesterreich, S., Deng, W., Jiang, S., Cui, X., Ivanova, M., Schiff, R., Kang, K., Hadsell, D.L., Behrens, J., Lee, A.V. 2003. Estrogen-mediated down-regulation of E-cadherin in breast cancer cells. Cancer Research. 63:5203-5208. Interpretive Summary: A common change that is observed in cancer is that of cell-cell interactions. These interactions occur through the binding of specific proteins on cells referred to as adhesion molecules. The progression from a normal state to a tumor state is often linked to reduced cell-cell interactions and reduced expression of these adhesion molecules on the cancer cell. In this study we show that expression of the adhesion protein, E-cadherin, is decreased in both normal and cancer cells by treatment of those cells with estrogen. This reduction was reversed by treatment of these cell with estrogen-blocking compounts. These effects of estrogen were demonstrated to be associated with the presence of specific estrogen-responsive transcription factors that bind to the E-cadherin gene. This work revealed a new regulatory mechanism for the regulation of cell adhesion through estrogen.
Technical Abstract: E-cadherin is an important mediator of cell-cell interactions, and has been shown to play a crucial role in breast tumor suppression. Its inactivation occurs through instability at its chromosomal locus and mutations, but also through epigenetic mechanisms such as promoter hypermethylation and transcriptional silencing. We show here that the potent mitogen estrogen causes down-regulation of E-cadherin levels in both normal and tumorigenic breast epithelial cells, and that this down-regulation is reversed by antiestrogens. The reduction in E-cadherin levels is via a decrease in promoter activity and subsequent mRNA levels. Chromatin immunoprecipitation assays revealed that estrogen receptor and corepressors were bound to the E-cadherin promoter, and that overexpression of corepressors, such as scaffold attachment factor B resulted in enhanced repression of E-cadherin. We propose that estrogen-mediated down-regulation of E-cadherin is a novel way of reducing E-cadherin levels in estrogen receptor-positive breast cancer.