A Keirsebilck, L Van Hoorde, Y Gao, G De Bruyne, E Bruyneel, P Vermassen, M Mareel, F van Roy
{"title":"同源小鼠侵袭性肿瘤形成过程中转染E-cadherin cDNA下调的机制。","authors":"A Keirsebilck, L Van Hoorde, Y Gao, G De Bruyne, E Bruyneel, P Vermassen, M Mareel, F van Roy","doi":"10.1159/000024498","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 1","pages":"44-56"},"PeriodicalIF":0.0000,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024498","citationCount":"24","resultStr":"{\"title\":\"Mechanisms of downregulation of transfected E-cadherin cDNA during formation of invasive tumors in syngeneic mice.\",\"authors\":\"A Keirsebilck, L Van Hoorde, Y Gao, G De Bruyne, E Bruyneel, P Vermassen, M Mareel, F van Roy\",\"doi\":\"10.1159/000024498\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":14452,\"journal\":{\"name\":\"Invasion & metastasis\",\"volume\":\"18 1\",\"pages\":\"44-56\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1998-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1159/000024498\",\"citationCount\":\"24\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Invasion & metastasis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1159/000024498\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Invasion & metastasis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000024498","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Mechanisms of downregulation of transfected E-cadherin cDNA during formation of invasive tumors in syngeneic mice.
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.