國家衛生研究院 NHRI:Item 3990099045/6134
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    題名: B cell-activating factor of TNF family (BAFF) signaling pathway is associated with Helicobacter Pylori-independent growth of gastric MALT lymphoma without T(11;18)(q21;q21)
    作者: Kuo, S;Chen, L;Yeh, K;Lin, C;Wu, M;Hsu, P;Tzeng, Y;Jeng, H;Cheng, A
    貢獻者: National Institute of Cancer Research
    摘要: Background: We have recently discovered that nuclear expression of BCL10 or NF-uB is closely associated with Helicobacter pylori (HP)-independent status of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with or without t(11;18)(q21;q21) (Blood. 2005;106:1037–1041). In this study, we examined the role of B cellactivating factor belonging to the TNF family (BAFF) in mediating BCL10 nuclear translocation and in activating NF-uB, and HP-independence of gastric MALT lymphoma without t(11;18)(q21;q21). Materials and Methods: Sixty-six patients who underwent successful HP eradication for localized low-grade gastric MALT lymphomas were included. Status of t(11;18)(q21;q21) was determined by reverse transcriptase polymerase chain reaction for API2-MALT1 transcript, while expression of BCL10, NF-uB, and BAFF was detected by immunohistochemistry. The primary MALT lymphoma cell was obtained from fresh marrow aspirationderived lymphoma of a t(11;18)(q21;q21)- and t(1;14)(p22;q32)-negative gastric MALT lymphoma patients who had failed antibiotics treatment and standard chemotherapy. Phospho-Akt (Ser473 and Thr308), BCL3, BCL10, NF-uB (p65), NF-uB (p52), cyclin D3, c-Myc, and BAFF protein expression were assessed by immunoblotting. Transactivity of NF-uB was measured by electromobility shift assay, Results: Fifty-two (78.8%) patients were negative for t(11;18)(q21;q21); among them, 34 (65.4%) were HP-dependent and 18 (34.6%) were HPindependent. Furthermore, in t(11;18)(q21;q21)-negative patients, BAFF expression was significantly higher in HP-independent than in HPdependent tumours (13 of 18 [72.2%] vs 10 of 34 [29.4%]; P = .003). BAFF overexpression was associated with nuclear expression of BCL3 (P = .014), BCL10 (P = 0.006), and NF-uB (P = 0.008). In MALT lymphoma cell line, BAFF activated NF-uB and AKT; the activated NF-uB up-regulated BCL10, c-Myc, and cyclin D3, and the activated AKT caused formation of BCL10/BCL3 complexes that translocated to the nucleus. Inhibition of AKT by LY294002 (a PI3K inhibitor) blocked BCL10 and BCL3 nuclear translocation, NF-uB transactivity, and BAFF expression. The BCL3 nuclear translocation and NF-uB activation were inhibited by silencing BCL10 (BCL10 SiRNA). In addition, knockdown of BCL3 expression by SiRNA influenced the nuclear translocation of BCL10. Conclusions: Our results indicate that BAFF-induced inflammationrelated signal transduction can lead to BCL10 nuclear translocation and NF-uB activation. The autocrine BAFF signal transduction pathway may contribute to the HP-independence of gastric MALT lymphoma without t(11;18)(q21;q21).
    日期: 2011-09
    關聯: European Journal of Cancer. 2011 Sep;47(Suppl 1):S648-S649.
    Link to: http://dx.doi.org/10.1016/S0959-8049(11)72497-2
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0959-8049&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000295752802292
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