Structural analysis of the C-CAM1 molecule for its tumor suppression function in human prostate cancer

✍ Scribed by Hsieh, Jer-Tsong; Earley, Karen; Pong, Rey-Chen; Wang, Yan; Van, Nguyen T.; Lin, Sue-Hwa

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 387 KB
• Volume: 41
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19990915)41:1<31::aid-pros5>3.0.co;2-p

✦ Synopsis

BACKGROUND.

Recently, we demonstrated that expression of C-CAM1, an immunoglobulin (Ig)-like cell adhesion molecule (CAM), was diminished in both prostate intraepithelial neoplasia and cancer lesions, indicating that loss of C-CAM1 expression may be involved in the early events of prostate carcinogenesis. Also, increased C-CAM1 expression can effectively inhibit the growth of prostate cancer. Structurally, C-CAM1 represents a unique CAM with a potential signal transducing capability. In this study, we further analyzed the functional domain of C-CAM1 for controlling its tumor suppression function. METHODS. Recombinant adenoviruses expressing a series of C-CAM1 mutants were generated, such as AdCAMF488 (mutated C-CAM1 containing Tyr-488 → Phe-488), Ad-CAMH458 (intracellular domain deletion mutant containing 458 amino acids), AdCAMG454 (intracellular domain deletion mutant containing 454 amino acids), and AdCAM⌬D1(C-CAM1 mutant containing first Ig domain deletion). After in vitro characterization of each virus, human prostate cancer cells infected with these viruses were subcutaneously injected into athymic mouse. Both tumor incidence and volume were measured for determining the tumor suppression function for each mutant. RESULTS. In vivo tumorigenic assay indicated that AdCAM⌬D1 without cell adhesion function still retained its tumor suppression activity. In contrast, both AdCAMH458 and AdCAMG454 decreased or lost their tumor suppression activity. CONCLUSIONS. Our data indicate that the intracellular domain of the C-CAM1 molecule is critical for inhibiting the growth of prostate cancer, suggesting that C-CAM1 interactive protein(s) may dictate prostate carcinogenesis.