Abstract 4650: A novel c-Myc target gene, Mina53, is a favorable prognostic marker in early stage of lung cancer

Abstract

Abstract Mina53, a novel target gene of c-Myc, is overexpressed in various malignancies. Overexpression of Mina53 has been associated with poor prognosis in esophageal cancer, renal cell carcinoma, and neuloblastoma. We previously demonstrated that Mina53 is overexpressed in lung cancer patients from the early clinical stages. In addition, the enforced expression of Mina53 in NIH/3T3 cells, a mouse fibroblast cell line, induces cell transformation, and Mina53 transfected NIH/3T3 clones produce tumors in nude mice. In this study, we examined the association between disease prognosis and Mina53 expression in lung cancer patients. Statistical analysis using the Kaplan-Meier method showed that patients with negative staining for Mina53 had significantly shorter survival than patients with positive staining for Mina53, especially in stage I or with squamous cell carcinoma. We hypothesized that Mina53 exerts different effects according to cancer cell type, inhibiting tumor progression in lung cancer cells. Because the major cause of death in lung cancer patients after surgery is distant metastasis, the effects on cell proliferation, cell cycle, apoptosis and cancer cell invasiveness were analyzed for the mechanisms involved in the association with favorable outcome. Growth of A549, a lung adenocarcinoma cell line, transfected with pCAGGS/mina53 (expression plasmid) was inhibited. On the contrary, the growth of NIH/3T3 transfected with pCAGGS/mina53 was not altered compared to those with pCAGGS (control). To investigate the mechanisms of reduced growth rate in A549, cell cycle analysis was performed using FACS analysis. After transfection of pCAGGS/mina53 into A549, pre-G0/G1 phase cells increased in a time-dependent manner. In addition, early apoptotic cells were more frequently observed among cells transfected with pCAGGS/mina53 than those with pCAGGS. Because cell growth inhibition associated with apoptosis was not observed in H226B, a lung squamous cell carcinoma cell line, we examined the possibility of an effect of Mina53 on cancer cell invasion. Number of migrating cells did not differ between pCAGGS/mina53 and pCAGGS transfected cells. The number of invading cells transfected with pCAGGS/mina53 significantly decreased compared with those with pCAGGS, whereas transfection with mina53 shRNA increased the number of invading cells. Considering the results mentioned above, overexpression in non-transformed cells induces cell transformation and tumorigenicity, whereas in lung cancer cells inhibits cell invasion and induces apoptosis. It is possible that the role of Mina53 differs between non-transformed cells and cancer cells, as well as cancer cell type. In overt lung cancer, Mina53 inhibits distant metastasis, so clarifying the signaling of Mina53 could be helpful in developing a strategy for preventing or limiting cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4650.