Anti-DEF6 monoclonal antibody, clone 4D5

Interferon regulatory factor-4 binding protein (IBP) is as a type of. GTPase suggested to serve an important role in tumor occurrence and development through the effects of cytoskeletal remodeling, and cell conduction mechanism. IBP is widely expressed in the immune system and expressed in several types of tumors. However, its expression and prognostic value in epithelial ovarian carcinoma (EOC) remain unclear. The present study aimed to investigate the expression of IBP in EOC, and its effect on clinicopathological variables and prognosis. A total of 107 and 30 cases of epithelial ovarian carcinoma and benign ovarian disease tissue sections, respectively, were examined using immunohistochemistry. The results indicated that the IBP expression status was negative or markedly weak in normal tissues, but highly expressed in EOC tissues. A significant association was observed between IBP overexpression and various clinicopathological factors, including advanced International Federation of Gynecology and Obstetrics stage (P<0.001), poor histologic grade (P=0.002), peritoneal carcinomatosis (P<0.001), lymph-node metastasis (P=0.023) and recurrence (P<0.001). Multivariate Cox regression analysis additionally suggested that IBP overexpression was an independent factor affecting recurrence-free survival [hazard ratio (HR)=4.099; 95% confidence interval (CI), 2.209-7.606; P<0.001) and overall survival (HR=2.317; 95% CI, 1.484-3.617; P<0.001) in patients with EOC. The results of the present study demonstrated that IBP overexpression may be associated with tumor development and progression in EOC, and therefore may serve as a novel target for treating this disease.

Many proteins that are aberrantly expressed in malignant tumors play important roles in promoting tumorigenesis, metastasis and immune escape. IFN regulatory factor 4-binding protein (IBP), which is a novel PH-DH-like protein related to SWAP-70, and functions as an upstream activator of Rho GTPases. It is widely expressed in cells of the immune system and is involved in coupling activated cell receptors to downstream signaling events that mediate cell proliferation, differentiation and polarization. Although IBP was detected in human chondrosarcoma, its function in tumor cells remains unknown. In this study, newly generated monoclonal anti-IBP antibodies were employed and they detected higher level expression of IBP in some human invasive breast carcinoma tissues and in two breast cancer cell lines that form highly invasive tumors in nude mice. In contrast, the levels of IBP mRNA and protein were low or undetectable in normal human breast tissues, benign breast lesions or low-tumorigenic breast cancer cell lines. over-expression of wild-type IBP in an IBP-negative breast cancer cell line markedly increased its proliferation and invasiveness in vitro. Conversely, RNA interference-mediated knockdown of IBP expression in an IBP-positive breast cancer cell line significantly reduced cell growth and invasiveness. Our results indicate that IBP is expressed in more highly invasive human breast cancer cells, such as MCF-7 and MDA-MB-231, with lower expression in normal breast tissue, benign tumors and less aggressive breast cancer cells, such as SKBR3 and MDA-MB-453. Thus, expression of IBP is correlated with the degree of malignant breast tumors. Nevertheless, it should be pointed our that further study with more tumor types is required to fully elucidate the role of IBP in tumorigenesis and the potential of IBP as a marker for more highly malignant tumors. (C) 2009 Elsevier B.V. All rights reserved.