Structural analysis of the C-CAM I molecule for its tumor suppression function in human prostate cancer

BACKGROUND. Recently, we demonstrated that expression of C-CAM1, an immunog lobulin (Ig)-like cell adhesion molecule (CAM), was diminished in both pros tate intraepithelial neoplasia and cancer lesions, indicating that loss of C-CAM1 expression may be involved in the early events of prostate carcinoge nesis. Also, increased C-CAM1 expression can effectively inhibit the growth of prostate cancer. Structurally, C-CAM1 represents a unique CAM with a po tential signal transducing capability. In this study, we further analyzed t he functional domain of C-CAM1 for controlling its tumor suppression functi on. METHODS. Recombinant adenoviruses expressing a series of C-CAM1 mutants wer e generated, such as AdCAMF488 (mutated C-CAM1 containing Tyr-488 --> Phe-4 88), AdCAMH458 (intracellular domain deletion mutant containing 458 amino a cids), AdCAMG454 (intracellular domain deletion mutant containing 454 amino acids), and AdCAM Delta D1(C-CAM1 mutant containing first Ig domain deleti on). After in vitro characterization of each virus, human prostate cancer c ells infected with these viruses were subcutaneously injected into athymic mouse. Both tumor incidence and volume were measured for determining the tu mor suppression function for each mutant. RESULTS. In vivo tumorigenic assay indicated that AdCAM Delta D1 without ce ll adhesion function still retained its tumor suppression activity. In cont rast, both AdCAMH458 and AdCAMG454 decreased or last their tumor suppressio n activity. CONCLUSIONS. Our data indicate that the intracellular domain of the C-CAM1 molecule is critical for inhibiting the growth of prostate cancer, suggesti ng that C-CAM1 interactive protein(s) may dictate prostate carcinogenesis. Prostate 41:31-38, 1999. (C) 1999 Wiley-Liss, Inc.