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Regulatory mechanisms controlling human E-cadherin gene expression

Oncogene volume 24, pages 8277–8290 (2005)Cite this article

Abstract

In cancer cells, loss of E-cadherin gene expression caused dysfunction of the cell–cell junction system, triggering cancer invasion and metastasis. Therefore, E-cadherin is an important tumor-suppressor gene. To understand how E-cadherin gene expression is regulated in cancer cells, we have used E-cadherin-positive and -negative expressing cells to find out the possible up- or downregulating transcription factors in human E-cadherin regulatory sequences. Functional analysis of human E-cadherin regulatory sequences constructs indicated that AML1, Sp1, and p300 may play important roles in promoting E-cadherin expression. In addition, we found there are four HNF3-binding sites in human E-cadherin regulatory sequences. The exogenous HNF3 can enhance the E-cadherin promoter activity in metastatic breast cancer cells and the metastatic breast cancer cells stably transfected with HNF3 showed re-expression of E-cadherin. The HNF3 stable transfectants changed from mesenchymal-like into epithelial morphology. The transwell assays showed the re-expressed E-cadherin reduced cell motility of metastatic breast cancer cells. These results suggested HNF3 may play important roles in the upregulation of the E-cadherin promoter, with the consequent re-expression of E-cadherin, thus reducing the metastatic potential of breast cancer cells. These findings suggested HNF3 plays important roles in the upregulation of the E-cadherin gene and may be able to reduce the motility of metastatic breast cancer cells.

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Acknowledgements

We acknowledge the technical assistance of GW Ruan, YC Liao, GJ Chen, and YS Chang. We also thank Dr H Miyoshi, Dr Han Zon Lee, and Dr Yue Li Juang for providing reagents, and members of the Chen lab for discussions and suggestions. This work was supported by Grants NSC 91-2745-B-320-001 and NSC 91-23320-B-320-012 from the National Science Council, Taiwan and Tzu Chi Foundation.

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Authors and Affiliations

  1. Graduate Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan

    Yan-Nan Liu & Ji Hshiung Chen

  2. Graduate Institute of Molecular and Cellular Biology, Tzu Chi University, Hualien, Taiwan

    Wen-Wen Lee, Chun-Yi Wang, Tung-Hui Chao & Ji Hshiung Chen

  3. Department of Life Science, Tzu Chi University, Hualien, Taiwan

    Yvan Chen & Ji Hshiung Chen

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  1. Yan-Nan Liu
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Correspondence to Ji Hshiung Chen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Liu, YN., Lee, WW., Wang, CY. et al. Regulatory mechanisms controlling human E-cadherin gene expression. Oncogene 24, 8277–8290 (2005). https://doi.org/10.1038/sj.onc.1208991

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