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NF-κB signaling regulates cell-autonomous regulation of CXCL10 in breast cancer 4T1 cells
진원종,김봉준,김다롱,추해영박,김홍희,하현일,이장희 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells. Treatment of 4T1 cells with CXCL10 increased the expression of P65, a subunit of the NF-κB pathway, via activation of the NF-κB transcriptional activity. Ectopic overexpression of P65 increased CXCL10 secretion and blunted JN-2-induced suppression of CXCL10 secretion, whereas overexpression of IκBα suppressed CXCL10 secretion. These results indicate that the CXCL10/CXCR3 axis creates a positive feedback loop through the canonical NF-κB signaling pathway in 4T1 cells. In addition, treatment of osteoblasts with conditioned medium from JN-2-treated 4T1 cells inhibited the expression of RANKL, a crucial cytokine for osteoclast differentiation, which resulted in an inhibitory effect on osteoclast differentiation in the co-culture system of bone marrowderived macrophages and osteoblasts. Direct intrafemoral injection of 4T1 cells induced severe bone destruction; however, this effect was suppressed by the CXCR3 antagonist via downregulation of P65 expression in an animal model. Collectively, these results suggest that the CXCL10/CXCR3-mediated NF-κB signaling pathway plays a role in the control of autonomous regulation of CXCL10 and malignant tumor properties in breast cancer 4T1 cells.
FRP-콘크리트 합성 바닥판의 유지 · 보수에 관한 실험적 연구
진원종 ( Chin Won Jong ),김성태 ( Kim Sung Tae ),조정래 ( Cho Jeong Rae ),조근희 ( Cho Keun Hee ),김병석 ( Kim Byung Suk ) 한국구조물진단유지관리공학회 2004 한국구조물진단유지관리공학회 학술발표대회 논문집 Vol.8 No.2
Bridge deck is the element presenting the largest damage potentiality among the major structural members. In the previous study, a new-type of FRP-concrete composite bridge deck system is proposed. The proposed deck systems are fabricated by casting concrete above the FRP panel, which is used as formwork during the curing of concrete and works as a structural member combined with concrete during service life. In the previous study, behavior characteristics of the proposed deck system is experimentally studied, including two different types of sections. The deck systems were confirmed to have enough performance for bridge deck. In this study, maintenance and repair methods for the deck during the service life of bridge are investigated.