| First Author | Behrens J | Year | 1991 |
| Journal | Proc Natl Acad Sci U S A | Volume | 88 |
| Issue | 24 | Pages | 11495-9 |
| PubMed ID | 1763063 | Mgi Jnum | J:34510 |
| Mgi Id | MGI:81966 | Doi | 10.1073/pnas.88.24.11495 |
| Citation | Behrens J, et al. (1991) The E-cadherin promoter: functional analysis of a G.C-rich region and an epithelial cell-specific palindromic regulatory element. Proc Natl Acad Sci U S A 88(24):11495-9 |
| abstractText | The cell-cell adhesion molecule E-cadherin is specifically expressed in epithelia and is involved in the maintenance of the epithelial phenotype. Expression of E-cadherin is downregulated in many poorly differentiated carcinomas, which leads to higher motility and invasiveness of the cells. To examine the mechanisms that regulate tissue-specific expression, we have characterized the promoter of the E-cadherin gene. We found that an upstream fragment (positions -178 to +92) mediates strong expression of a chloramphenicol acetyltransferase reporter gene in epithelial cells (i.e., 60% of the level obtained with simian virus 40 promoter/enhancer constructs), whereas in nonepithelial cells this promoter was either inactive or much less active. By DNase I footprinting and gel retardation analysis as well as through functional dissection of the regulatory sequences, we identified two regions that contribute to tissue-specific activity of the promoter: (i) a G-C-rich region between -25 and -58 that generates basic epithelial promoter activity, most likely in combination with an initiator element present at the single transcription start site of the gene, and (ii) a palindromic sequence between -75 and -86 (named E-pal) that potentiates the activity of the proximal E-cadherin promoter and confers epithelial cell-specific activity on a simian virus 40 promoter. The E-pal sequence is homologous to cis regulatory elements active in keratin gene promoters and competes with these elements for nuclear factor binding. Interestingly, the activity of the E-cadherin promoter was reduced in dedifferentiated breast carcinoma cells, indicating that the identified elements are subject to negative regulation during tumor progression. |
