María Luisa M. Faraldo and Isabel Rodrigo contributed equally to this work.
Analysis of the E-cadherin and P-cadherin promoters in murine keratinocyte cell lines from different stages of mouse skin carcinogenesis
Article first published online: 7 DEC 1998
Copyright © 1997 Wiley-Liss, Inc.
Volume 20, Issue 1, pages 33–47, September 1997
How to Cite
Faraldo, M. L. M., Rodrigo, I., Behrens, J., Birchmeier, W. and Cano, A. (1997), Analysis of the E-cadherin and P-cadherin promoters in murine keratinocyte cell lines from different stages of mouse skin carcinogenesis. Mol. Carcinog., 20: 33–47. doi: 10.1002/(SICI)1098-2744(199709)20:1<33::AID-MC5>3.0.CO;2-J
- Issue published online: 7 DEC 1998
- Article first published online: 7 DEC 1998
- Manuscript Accepted: 14 MAY 1997
- Manuscript Revised: 28 APR 1997
- Manuscript Received: 2 DEC 1996
- cadherin expression;
- tumor progression;
- nuclear factors;
- regulatory elements
We previously isolated the 5′ upstream sequences of the mouse P-cadherin gene, in which putative binding sites for several transcription factors were identified between nt –101 and +30. In the study reported here, the promoter activity of the postulated 5′ cis-acting sequences of the P-cadherin promoter, and the activity of the proximal E-cadherin promoter were investigated in several murine keratinocyte cell lines showing different levels of P- and E-cadherin expression as well as different morphology and tumorigenic behavior. Cell-type specificity and optimal activity of P-cadherin expression in murine keratinocytes was conferred by 5′ sequences located between nt –200 and +30, and the GC-rich region (nt –101 to +80) and a CCAAT box element (nt –65) had a major regulatory role. The cell-type specificity of the E-cadherin promoter, on the other hand, was mediated by a combination of positive regulatory elements, a GC-rich region (nt –58 to –24), and a CCAAT box (nt –65) and repressor elements inside the E-pal sequence. Interestingly, the maximum repressor effect of the E-pal element was observed in non-expressing undifferentiated spindle cells. In vitro binding studies indicated that the GC-rich region of the P-cadherin promoter was mainly recognized by Sp1-related nuclear factors, whereas both AP2- and Sp1-related factors were involved in the interaction of the GC-rich region of the E-cadherin promoter. Common factors (probably related to the CP1 family) seemed also to be involved in the recognition of the CCAAT-box element of both the E- and P-cadherin promoters, but additional specific factors participated in the interaction with the CCAAT box of the E-cadherin promoter. Our studies also support the hypothesis that loss or modification of some of the regulatory factors occurs during mouse skin tumor progression. Mol. Carcinog. 20:33–47, 1997. © 1997 Wiley-Liss, Inc.