Abstract 4047: TRIM32 facilitates cell growth, migration and anti-apoptosis

Abstract Introduction: Tripartite motif (TRIM) proteins are characterized by the presence of a RING finger, one or two zinc-binding motifs named B-boxes and an associated coiled-coil region. Most TRIM proteins have been reported to have a role in the ubiquitination process. Furthermore, several TRIM family members are involved in various cellular processes such as transcriptional regulation, cell growth, apoptosis, development and oncogenesis. TRIM32 also has a RING-finger domain and functions as an E3-ubiquitin ligase. In the previous study, it has been reported that TRIM32 protein expression is elevated in a mouse skin carcinogenesis model and in human skin squamous cell carcinoma and TRIM32 mRNA expression is elevated in human head and neck squamous cell carcinoma. However, the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we studied the function of TRIM32 in the progression of carcinogenesis. Methods: We established the cell lines overexpressed TRIM32 wild type and the deletion mutant of the RING-finger domain by the infection of retrovirus vectors. Using these cell lines, we analyzed the effect of TRIM32 on cell growth, transforming activity, cell motility and apoptosis induced by cisplatin. Additionally, we investigated whether siRNA for TRIM32 effects on these functions. Furthermore, we examined the expression level of TRIM32 protein in oral carcinoma samples using immunohistochemical method and analyzed the relationship between TRIM32 and clinical presentation. Results: Overexpression of TRIM32 promoted cell growth, transforming activity and cell motility, whereas a dominant negative mutant of TRIM32 lacking the RING-finger domain inhibited these effects. In addition, we found that TRIM32 suppressed apoptosis induced by cisplatin in HEp2 cell lines, originating from human laryngeal squamous cell carcinoma. In contrast, siRNA for TRIM32 suppressed cell proliferation, cell motility and anti-apoptosis. In clinical research, a high-expression group of TRIM32 presented more advanced stage (clinical stage, T stage and neck lymph node metastasis) than a low-expression group. Conclusions: In this study, our experimental results in vitro were supported by clinical research. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis and resistance to anti-cancer drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4047. doi:10.1158/1538-7445.AM2011-4047