MECHANISMS OF INACTIVATION OF E-CADHERIN IN BREAST-CANCER CELL-LINES

Loss of E-cadherin (CDH1) function is thought to contribute to progres sion in breast cancer and other solid tumors by increasing proliferati on, invasion, and/or metastasis. In some cases, the restoration of CDH 1 function may be an important therapeutic option. This possibility wi ll depend on the mechanism by which CDH1 is inactivated. Here we prese nt analyses of CDH1 expression, genetic mutation, and promoter methyla tion in CDH1 in 10 commonly used breast cancer cell lines. Five cell L ines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D) expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB-13 4 IV, CAMA1, and MDA-MB-435) did not express CDH1, Fluorescence in sit u hybridization analyses of each of these cell lines showed evidence f or the physical deletion of one allele of CDH1, and three cell lines w ere found to carry homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon 6 was deleted in MDA-MB-134 TV cells, a nd 600 MPE cells carried a 21-bp deletion in the splicing acceptor sit e for exon 9. CAMA1 seemed to have been inactivated through promoter m ethylation No explanation was found for the inactivation of CDH1 in MD A-MB-435.