ROLE OF E BOXES IN THE REPRESSION OF E-CADHERIN EXPRESSION

Decreased expression of the intercellular adhesion molecule E-cadherin correlates with tumor aggressiveness and invasion capacity of cell li nes. The decrease of E-cadherin expression results primarily from redu ced mRNA expression. We show here that the ac tivity of a human E-cadh erin promoter construct is cell specific and correlates with E-cadheri n mRNA expression. This spectrum of activity is conserved by a region as short as 81 bp obtained after 5' deletion. Mutation analysis reveal ed that two E box elements of this minimal promoter are involved in th e silencing of E-cadherin promoter activity occurring in cancer cells. E boxes are mainly known as tar,aet sequences for bHLH transcription factors that are involved in the control of tissue differentiation and are antagonised by HLH proteins. However, mutation data and cotransfe ction experiments using HLH protein expression vectors indicate that b HLH transcription factors are not significantly involved in the E box mediated silencing of this E-cadherin promoter fragment. (C) 1997 Acad emic Press.