908P - Nuclear Expression of Bcl10 Has a Role in the Regulation of Cell Growth of Ovarian Cancer Through the Activation of Nf-&Kgr;B‐Dependent Cyclin D1 Signaling

Abstract

ABSTRACT Aim: We previously characterized the molecular linkage that directs both BCL10 overexpression and nuclear translocation in response to inflammation-related NF-kB signaling pathway in breast cancer cell line, lymphoma cell line, and cervical cancer line (J Biol Chem 2006;281:167-75, Blood 2008;112:2927-34; Gynecol Oncol 2012;126:245-51). Since NF-kB activation has been shown to occur in the pathogenesis of ovarian cancer, we sought to investigate whether BCL10 possesses clinical significance in relation to ovarian cancer. Methods: Two ovarian cancer cell lines (SK-OV3, and CAOV-3) with overexpressing BCL10 were used in this study. The proliferation effect of BCL10 and its mechanism were evaluated in vitro and in vivo. The DNA binding activity of NF-kB was determined by the luciferase assay. The expression of BCL10, NF-kB, and cyclin D1 in tumor cells from an array of 100 tissue samples was examined using immunohistochemical staining. Results: We found that inhibition of BCL10 with BCL10 small interfering RNA (siRNA) significantly reduced the cell growth rate of these two ovarian cancer cell lines through the G1 arrest. BCL10 siRNA treatment inhibited the expression of p-IKKb and p-IkB, and also down-regulated NF-kB activation and its downstream cell cycle protein, cyclin D1. Furthermore, we used BCL10 short hairpin RNA (shRNA) plasmids to transfect two ovarian cancer cell lines, and found that the down-regulation of BCL10 inhibited the tumor growth rate of ovarian cancer and prolonged the survival rate in xenograft model of immunodeficient mice (SK-OV3: 38.7 ± 4.4 in WT; 59.2 ± 6.2 in BCL10 knockdown, and CAOV-3: 37.2 ± 7.8 in WT; 76.7 ± 11.6 in BCL10 knockdown). In tissue samples, we detected that serous cystadenocarcinoma had a higher rate of BCL10 nuclear expression (35/49 [71.4%]) than mucinous cystadenocarcinoma (4/18 [22.2%]) and endometrioid adenocarcinoma (16/28 [57.1%]) (P = 0.001). BCL10 nuclear expression was also closely associated with tumor grading (P = 0.017). Furthermore, nuclear expression of BCL10 was closely associated with nuclear NF-kB expression (P Conclusions: Our findings indicate that nuclear BCL10 plays an important role in controlling the growth and progression of ovarian cancer cells through NF-kB dependent cyclin D1 regulation. Disclosure: All authors have declared no conflicts of interest.