Yoo B C, Hong S-H, Ku J-L, Kim Y-H, Shin Y-K, Jang S-G, Kim I-J, Jeong S-Y, Park J-G
Research Institute, National Cancer Center, Madu2-dong, Goyang-si, 410-769, Gyeonggi-do, Korea.
Cell Mol Life Sci. 2009 Jan;66(2):350-64. doi: 10.1007/s00018-009-8562-3.
Comparative analysis of proteomes using 5-fluorouracil (5-FU)-resistant human colon cancer cell line revealed that decreased galectin-3 expression was significantly associated with retarded proliferation. However, in the presence of 5-FU proliferation rate of cells with suppressed galectin-3 expression did not differ from that of cells with normal galectin-3 expression, even galectin-3 suppression augmented apoptosis. Mechanism by which galectin-3 regulates cancer cell proliferation has been identified in immunoprecipitates of the anti-galectin-3 antibody. Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) was identified as a protein interacting with galectin-3. Interestingly, while galectin-3 protein was not affected by the hnRNP Q level, its suppression was accompanied by a decrease in hnRNP Q expression. The present study demonstrates that galectin-3 stabilizes hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU.
使用5-氟尿嘧啶(5-FU)耐药的人结肠癌细胞系对蛋白质组进行比较分析发现,半乳糖凝集素-3表达降低与增殖迟缓显著相关。然而,在5-FU存在的情况下,半乳糖凝集素-3表达受抑制的细胞的增殖速率与半乳糖凝集素-3表达正常的细胞并无差异,甚至半乳糖凝集素-3抑制会增强细胞凋亡。在抗半乳糖凝集素-3抗体的免疫沉淀物中已确定半乳糖凝集素-3调节癌细胞增殖的机制。异质性核糖核蛋白Q(hnRNP Q)被鉴定为与半乳糖凝集素-3相互作用的一种蛋白质。有趣的是,虽然半乳糖凝集素-3蛋白不受hnRNP Q水平的影响,但其抑制伴随着hnRNP Q表达的降低。本研究表明,半乳糖凝集素-3通过形成复合物来稳定hnRNP Q,而hnRNP Q水平的降低会导致增殖缓慢以及对5-FU的敏感性降低。