Decreased expression of the Ca(2+)-dependent cell adhesion molecule E-cadherin is observed in several poorly differentiated carcinomas and is presumably associated with an invasive phenotype of these tumors. Evidence accumulated so far indicates that decreased transcription is a major mechanism leading to defective E-cadherin function. Therefore, we isolated and characterized the human E-cadherin gene promoter and studied the transcriptional regulation of this gene in two human prostate cancer cell lines, one expressing E-cadherin (PC-3), the other one not expressing E-cadherin (TSU-pr1). We show that the E-cadherin promoter is not active in the non-expressing cells and that this may be due to the binding of a repressor protein to the promoter.