title: Mechanisms of downregulation of transfected E-cadherin cDNA during formation of invasive tumors in syngeneic mice.
abstract: Loss of E-cadherin expression has been observed both in experimental tumors and in human cancers and is related to invasiveness and poor differentiation. The E-cadherin-negative mouse mesenchymal tumor cell line MO4 was transfected with several plasmids expressing mouse E-cadherin cDNA. These plasmids differed from each other by the extent of E-cadherin-specific 3' untranslated region (UTR) sequences and by the use of different constitutive promoters. Transfectants were isolated that expressed functional E-cadherin in a homogeneous way. In syngeneic mice, such MO4-Ecad transfectants invariably produced malignant fibrosarcoma-like tumors, which were completely E-cadherin-negative at the protein level. Northern blotting revealed that E-cadherin mRNA expression was downregulated in some but not all MO4-Ecad tumors. Downregulation was caused by mRNA instability triggered by particular 3' UTR sequences. This in vivo downregulation of E-cadherin in malignant MO4-Ecad tumors turned out to be reversible and is likely to be mediated by host factors to be further identified.
authors: Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, Belgium.
authors: A
authors: A
authors: Keirsebilck
authors: L
authors: L
authors: Van Hoorde
authors: Y
authors: Y
authors: Gao
authors: G
authors: G
authors: De Bruyne
authors: E
authors: E
authors: Bruyneel
authors: P
authors: P
authors: Vermassen
authors: M
authors: M
authors: Mareel
authors: F
authors: F
authors: van Roy
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015820:Cadherins / Q000096:biosynthesis* / Q000502:physiology; D018076:DNA, Complementary; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D051379:Mice; D009361:Neoplasm Invasiveness; D011233:Precipitin Tests; D012333:RNA, Messenger; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D018076:DNA, Complementary; D012333:RNA, Messenger