1. ¹Graduate Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
2. ²Graduate Institute of Molecular and Cellular Biology, Tzu Chi University, Hualien, Taiwan
3. ³Department of Life Science, Tzu Chi University, Hualien, Taiwan

Correspondence: JH Chen, Graduate Institute of Molecular and Cell Biology, College of Life Sciences, Tzu Chi University, 701 Chung Yang Road Sec 3, Hualien 970, Taiwan. E-mail: jhc@mail.tcu.edu.tw

Received 20 February 2005; Revised 28 June 2005; Accepted 30 June 2005; Published online 22 August 2005.

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.