Regulatory mechanisms controlling human E-cadherin gene expression.
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 down regulating 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.
Liu
Yan-Nan
YN
Graduate Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Lee
Wen-Wen
WW
Wang
Chun-Yi
CY
Chao
Tung-Hui
TH
Chen
Yvan
Y
Chen
Ji Hshiung
JH
D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002843:Chromatin / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000502:physiology*; D045325:HCT116 Cells; D051536:Hepatocyte Nuclear Factors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism
D015820:Cadherins; D002843:Chromatin; D050676:Core Binding Factor Alpha 2 Subunit; D051536:Hepatocyte Nuclear Factors; C493728:RUNX1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors