EBAG9/RCAS1 expression enhances tumor growth in renal cell carcinoma

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Introduction and Objectives : The EBAG9 was previously identified as an estrogen responsive gene, and it was lately revealed that the EBAG9 is identical with RCAS1 which induces apoptosis of immune cells such as T, B, and NE cells, and which allows tumor cells to escape of tumors from immune surveillance. In this study, we provide evidence that EBAG9/RCAS1 may modulate the potential mechanism of tumor progression using animal models.Methods : We compared the cell growth of human EBAG9-transfected renca cells with empty vector-transfected renca clones in vitro and in vivo. We further examined expression of EBAG9/RCAS1 immunohistochemically in 78 renal cell carcinoma specimens. We statistically analyzed correlation between EBAG9/RCAS1 expression and clinicapathological characteristics.Results : Overexpression of EBAG9 had no stimulatory effect on the growth of renca clones in cell culture. On the other hand EBAG9-transfected renca cells implanted in the flank of Balb/c mice established s … More ignificantly enlarged tumors compared with vector controls (1712.1±506.4 mm^3 vs. 366.2±110.1 mm^3, p=0.0055). Mice bearing tumors of EBAG9-transfected renca cells had significantly worse survival than animals bearing control tumors. Histological examination of EBAG9-expressing tumors grown in Balb/c mice did not show apoptotic lymphocytes positively stained by TUNEL assay. However, immunohistochemiclal analysis revealed the number of CD8 lymphocytes around tumors decreasing (10.0 vs. 5.8 /10HPF). These data suggested that EBAG9 expression in tumor cells may contribute to the suppression of immune response by inhibiting tumor-infiltrating CD8 lymphocytes without apoptosis. Immunohistochemical analysis showed that strong and diffuse immunostaining in the cytoplasm was identified in 68/78 (87.2%) of primary renal cell carcinoma cases. In contrast, weak-EBAG9/RCAS1 expression was observed in the adjacent normal tissue. Positive EBAG9/RCAS1 immunostaining in the primary cancers significantly correlated with advanced pathological T stages and vascular infiltration (p=0.0017 and p=0.0109, respectively). Patients with high EBAG9/RCAS1 immunoreactivity had significantly worse cancer-specific survival than those with low EBAG9/RCAS1 expression. Multivariate analysis revealed that high EBAG9/RCAS1 expression was an independent prognostic predictor for cancer-specific survival (p=0.0485).Conclusions : EBAG9/RCAS1 is expressed in the majority of human renal cell carcinomas and high EBAG9/RCAS1 immunoreactivity is associated with tumor aggressiveness and unfavorable prognosis. Less