SUPPRESSION OF TUMORIGENICITY OF BREAST-CANCER CELLS BY AN EPITHELIAL-CELL ADHESION MOLECULE (C-CAM1) - THE ADHESION AND GROWTH SUPPRESSIONARE MEDIATED BY DIFFERENT DOMAINS

C-CAM1 is an epithelial adhesion molecule of immunoglobulin supergene family and has been implicated in the growth suppression of prostate c ancer cells. Here we show that C-CAM1 can also suppress the tumorigeni city of breast cancer cells. These observations suggest that C-CAM1 ma y be a general growth suppressor in epithelial cells. In addition, we have identified the cytoplasmic domain, but not the extracellular adhe sion domain, of C-CAM1 as critical for the growth suppression. Thus, t he adhesion and the growth suppression functions of C-CAM1 are indepen dent of each other. Furthermore, mutation at the tyrosine phosphorylat ion site in the cytoplasmic domain of C-CAM1 did not obliterate C-CAM1 's growth suppression function, suggesting that tyrosine phosphorylati on is not involved in the signal transduction pathway leading to cell growth suppression. These studies provide the structural basis for fut ure development of therapeutics that may selectively activate C-CAM1's growth suppression function.