The ectopic expression of IFN regulatory factor 4-binding protein is correlated with the malignant behavior of human breast cancer cells.
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.
Li
Peng
P
Department of Clinical Biochemistry, Laboratory Sciences, Third Military Medical University, Chongqing 400038, PR China.
Zhang
Zhujun
Z
Wang
Qingliang
Q
Li
Shuhui
S
Zhang
Yang
Y
Bian
Xiuwu
X
Chen
An
A
Hu
Chuanmin
C
D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D015778:Minor Histocompatibility Antigens; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000517:prevention & control; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D050835:Interferon Regulatory Factors; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D020741:rho GTP-Binding Proteins; D000099218:Interferon Regulatory Factor-4; C491873:SWAP70 protein, human