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| PROGRESSION OF CARCINOMA-CELLS IS ASSOCIATED WITH ALTERATIONS IN CHROMATIN STRUCTURE AND FACTOR-BINDING AT THE E-CADHERIN PROMOTER IN-VIVO |
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| Author(s): HENNIG G, BEHRENS J, TRUSS M, FRISCH S, REICHMANN E, BIRCHMEIER W |
| Source: ONCOGENE Volume: 11 Issue: 3 Pages: 475-484 Published: AUG 3 1995 |
| Times Cited: 110 References: 54 |
| Abstract: E-cadherin has been identified as a tumor (invasion) suppressor gene, which is mutated in 50% of diffuse-type human gastric carcinomas. In other carcinomas, the expression of E-cadherin is down-regulated in the poorly differentiated cells such as from breast, bladder, lung and colon. We have here examined the in vivo properties of the genomic E-cadherin promoter in well and poorly differentiated carcinoma cell lines in order to gain insights into the mechanisms of E-cadherin downregulation in tumors. In vivo footprinting analysis revealed that positive regulatory elements of the E-cadherin promoter (a GC-rich region, the CCAAT-box and a palindromic element) are specifically bound by transcription factors in E-cadherin-expressing but not in non-expressing cells. The tested cell systems include more than a dozen carcinomas cell lines as well as mammary epithelial cells where E-cadherin expression can be switched off by activation of a Fos-estrogen receptor fusion protein and rhabdomyosarcoma cells where E-cadherin expression was induced by transfection with E1A. Mapping of DNase I hypersensitive sites showed that the chromatin structure in the promoter region is loosened in expressing but condensed in nonexpressing cells. Furthermore, the endogenous E-cadherin promoter is specifically methylated at CpG sites in the undifferentiated cells. We also show that the in vivo properties of the promoter in E-cadherin-negative carcinoma cells are similar as in mesenchymal cells, i.e. fibroblasts or sarcoma cells. These data suggest that silencing of the E-cadherin promoter during epithelial-mensenchymal transition and tumor progression is due to a loss of factor binding in vivo and to chromatin rearrangement in the regulatory region. |
| Document Type: Article |
| Language: English |
Addresses:
1. MAX DELBRUCK CENTRUM MOLEK MED, D-13125 BERLIN, GERMANY
2. INST MOLEK BIOL & TUMORFORSCH, D-35037 MARBURG, GERMANY
3. LA JOLLA CANC RES FDN, LA JOLLA, CA 92037 USA
4. SWISS INST EXPTL CANC RES, CH-1066 EPALINGES, SWITZERLAND |
| Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS |
| Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity |
| IDS Number: RN530 |
| ISSN: 0950-9232 |
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