Functional allelic loss detected at the protein level in archival human tumours using allele-specific E-cadherin monoclonal antibodies.

作者: Karl-Friedrich Becker , Elisabeth Kremmer , Manfred Eulitz , Stephan Schulz , Jörg Mages

DOI: 10.1002/PATH.1149

关键词:

摘要: Immunohistochemical analysis has been used to show that expression of the homophilic cell-to-cell adhesion molecule, E-cadherin, is frequently altered in human cancers, including gastric and breast carcinoma. Besides genetic down-regulation, structural mutations such as in-frame deletions exon 8 9 were found; these may affect binding monoclonal antibodies for immunohistochemical analysis. In this study it was found HECD-1 E9, two often E-cadherin immunoanalysis, react with epitopes present at least part 9, respectively. This generated characterized a mutation-specific antibody, E-cad delta 8-1, reacting mutant protein lacking but not wild-type molecule. By using 8-1 HECD-1, possible separately analyse immunoreactivity normal proteins, respectively, an allele-specific manner archival material. A similar performed E9 previously antibody 9-1. Typically, cancer harbouring splice site gene mutations, proteins expressed detected malignant tissues. These results indicate variant-specific can be identify differentially proteins. For different should exclude alterations resulting failure detect protein.

参考文章(35)
Strumane K, Cornelisse C, Nollet F, Cleton-Jansen Am, Berx G, van Roy F, de Leeuw Wj, E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene. ,vol. 13, pp. 1919- 1925 ,(1996)
Anne-Karina Perl, Petra Wilgenbus, Ulf Dahl, Henrik Semb, Gerhard Christofori, A causal role for E-cadherin in the transition from adenoma to carcinoma Nature. ,vol. 392, pp. 190- 193 ,(1998) , 10.1038/32433
William B. Isaacs, Stephen B. Baylin, Nancy E. Davidson, Jeremy R. Graff, James G. Herman, Rena G. Lapidus, Paula M. Pitha, Rosa Xu, Hemi Chopra, David F. Jarrard, E-Cadherin Expression Is Silenced by DNA Hypermethylation in Human Breast and Prostate Carcinomas Cancer Research. ,vol. 55, pp. 5195- 5199 ,(1995)
Meir Aridor, William E. Balch, Integration of endoplasmic reticulum signaling in health and disease. Nature Medicine. ,vol. 5, pp. 745- 751 ,(1999) , 10.1038/10466
Karl-Friedrich Becker, Ingrid Becker, Michael J. Atkinson, Jörg R. Siewert, Ulrike Reich, Hjalmar Nekarda, Heinz Höfler, E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Research. ,vol. 54, pp. 3845- 3852 ,(1994)
Parry Guilford, Justin Hopkins, James Harraway, Maybelle McLeod, Ngahiraka McLeod, Pauline Harawira, Huriana Taite, Robin Scoular, Andrew Miller, Anthony E. Reeve, E-cadherin germline mutations in familial gastric cancer Nature. ,vol. 392, pp. 402- 405 ,(1998) , 10.1038/32918
Setsuo Hirohashi, Masatoshi Takeichi, Yukio Shimosato, Masayuki Noguchi, Osahiko Abe, Shinji Hirano, Yutaka Shimoyama, Cadherin Cell-Adhesion Molecules in Human Epithelial Tissues and Carcinomas Cancer Research. ,vol. 49, pp. 2128- 2133 ,(1989)
Geert Berx, Karl-Friedrich Becker, Heinz Höfler, Frans van Roy, Mutations of the human E‐cadherin (CDH1) gene Human Mutation. ,vol. 12, pp. 226- 237 ,(1998) , 10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D
Gabriele Handschuh, Sonja Candidus, Birgit Luber, Ulrike Reich, Christina Schott, Sandra Oswald, Helma Becke, Peter Hutzler, Walter Birchmeier, Heinz Höfler, Karl-Friedrich Becker, Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility. Oncogene. ,vol. 18, pp. 4301- 4312 ,(1999) , 10.1038/SJ.ONC.1202790
Gerhard Christofori, Henrik Semb, The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene Trends in Biochemical Sciences. ,vol. 24, pp. 73- 76 ,(1999) , 10.1016/S0968-0004(98)01343-7