Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer

Abstract

Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription -polymerase chain reaction (RT -PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERa. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERa were evaluated by RT -PCR in 22 cases. The expression for EBAG9 and ERa was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P ¼ 0.0402) and advanced disease (P ¼ 0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P ¼ 0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (Po0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERa mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERa expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.

Modulation of Gene Expression by Tumor-Derived p53 Mutants

“…In vivo transcriptional changes induced by p53 mutants have also been reported previously by us and others (16). Of the genes identified in our microarray, MCL1 EBAG9, ANGPT1, ITGA6, NFB2, and E2F-5 expression has been reported as up-regulated in various cancer types (33)(34)(35)(36)(37)(38). Because information is not available in the literature, it remains to be seen whether these genes are up-regulated in the natural context of the p53 mutation, i.e., in human cancers carrying a p53 mutation.…”

Estrogen Receptor–Binding Fragment–Associated Antigen 9 Is a Tumor-Promoting and Prognostic Factor for Renal Cell Carcinoma

“…As we showed that there are several types of cancer that intensely express EBAG9 and the expression levels of EBAG9 may relate to advanced tumor grades (3)(4)(5)(6), it is likely that the tumorpromoting effect of EBAG9 is a general event in malignancies regardless of their estrogen dependency. We also observed the lack of association between sex and EBAG9 expression in human RCC in our clinicopathologic study (Supplementary Table 1).…”

EBAG9 Adds a New Layer of Control on Large Dense-Core Vesicle Exocytosis via Interaction with Snapin

“…EBAG9 is an estrogen-inducible, ubiquitously expressed protein with close homologues in human and murine rodents that exhibits a Golgi-predominant localization in nonneuronal cells Engelsberg et al, 2003). This raised the question of what function EBAG9 under physiological conditions has and whether this function relates to its proposed tumor association (Ikeda et al, 2000;Kubokawa et al, 2001;Suzuki et al, 2001;Tsuneizumi et al, 2001;Leelawat et al, 2003;Akahira et al, 2004). Using full-length EBAG9 as the bait to screen a human brain cDNA library, we identified Snapin as an interaction partner of EBAG9 and verified the relevance of this interaction in exocytosis assays.…”