目的 探討膜表面核仁素(nucleiolin,NCL)在表皮生長因子受體(epidermal growth factor receptor,EGFR)信號啟動中的作用。
方法 采用免疫組化法檢測NCL及EGFR在甲狀腺乳頭狀癌組織中的表達;Western blot法檢測甲狀腺乳頭狀癌細胞TPC-1中磷酸化EGFR (phosphorylation EGFR,p-EGFR)的表達水平;Transwell小室試驗檢測TPC-1細胞的遷移能力。
結果 免疫組化染色結果顯示,甲狀腺乳頭狀癌組織中NCL及EGFR的表達陽性率分別為100% (56/56)和80.4% (45/56); NCL及EGFR的表達與淋巴結轉移有關(P<0.05),且NCL的表達與EGFR的表達呈正相關關系(r=0.635,P<0.01)。Western blot法檢測結果顯示,拮抗甲狀腺乳頭狀癌TPC-1細胞的NCL或EGFR后,其p-EGFR表達水平均明顯下調(P<0.01)。Transwell小室試驗發(fā)現(xiàn),拮抗NCL和EGFR后,可明顯減少TPC-1細胞的穿膜細胞數(shù)(P<0.01)。
結論 膜表面NCL可能是EGFR受體信號啟動的必要成分,可能通過EGFR參與腫瘤的生長與轉移。以NCL為靶點將開拓腫瘤新的治療領域。
引用本文: 楊香山,范開席,李成軍,李愛萍,張晶,馮曼. 膜表面核仁素參與表皮生長因子受體信號啟動的研究. 中國普外基礎與臨床雜志, 2013, 20(10): 1117-1121. doi: 復制
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7. | Iliakis G, Krieg T, Guan J, et al. Evidence for an S-phase checkpoint regulating DNA replication after heat shock:a review[J]. Int J Hyperthermia, 2004, 20(2):240-249. |
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9. | 王慷慨, 肖獻忠. 核仁素在細胞增殖與細胞凋亡中的作用[J]. 中南大學學報:醫(yī)學版, 2004, 29(6):707-710. |
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11. | 蒙國照, 肖勝軍, 曾思恩, 等. 細胞表面核仁素表達下調抑制肝癌細胞生長[J]. 中華腫瘤學雜志, 2011, 33(1):23-27. |
12. | 田曉彩, 劉先領, 胡春宏. 核仁素表達下調對阿霉素所致乳腺癌細胞增殖抑制和凋亡的影響[J]. 中華腫瘤雜志, 2010, 32(4):271-272. |
13. | Huang Y, Shi H, Zhou H, et al. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin[J]. Blood, 2006, 107(9):3564-3571. |
14. | Christian S, Pilch J, Akerman ME, et al. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels[J]. J Cell Biol, 2003, 163(4):871-878. |
15. | Reyes-Reyes EM, Akiyama SK. Cell surface nucleolin is a signal transducing P-selectin binding protein for human colon carcin cells[J]. Exp Cell Res, 2008, 314(11-12):2212-2223. |
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17. | Harms G, Kraft R, Grelle G, et al. Identification of nucleolin as a new L-selectin ligand[J]. Biochem J, 2001, 360(Pt 3):531-538. |
18. | Krust B, El Khoury D, Nondier I, et al. Targeting surface nucle-olin with multivalent HB-19 and related Nucant pseudopeptides results in distinct inhibitory mechanisms depending on the malignanttumor cell type[J]. BMC Cancer, 2011, 11:333. |
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21. | 王曉艷, 沈守榮, 劉芬結, 等. 結腸癌中NGX6抑制EGFR/K-ras/JNK/c-Jun/cyclin D1信號通路的研究[J]. 生物化學與生物物理進展, 2008, 35(5):570-576. |
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27. | , 286(51):43816-43829. |
- 1. Tajrishi MM, Tuteja R, Tuteja N. Nucleolin:The most abundantmultifunctional phosphoprotein of nucleolus[J]. Commun Integr Biol, 2011, 4(3):267-275.
- 2. Ginisty H, Sicard H, Roger B, et al. Structure and functions of nucleolin[J]. J Cell Sci, 1999, 112(Pt6):761-772.
- 3. Orrick LR, Olson MO, Busch H. Comparison of nucleolar prot-eins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis[J]. Proc Natl Acad Sci USA, 1973, 70(5):1316-1320.
- 4. Kobayashi J, Fujimoto H, Sato J, et al. Nucleolin participates in DNA double-strand break-induced damage response through MDC1-dependent pathway[J]. PLoS One, 2012, 7(11):e49245.
- 5. Wang SA, Li HY, Hsu TI, et al. Heat shock protein 90 stabilizesnucleolin to increase mRNA stability in mitosis[J]. J Biol Chem,.
- 6. Ding Y, Song N, Liu C, et al. Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin[J]. Arterioscler Thromb Vasc Biol, 2012, 32(9):e126-e134.
- 7. Iliakis G, Krieg T, Guan J, et al. Evidence for an S-phase checkpoint regulating DNA replication after heat shock:a review[J]. Int J Hyperthermia, 2004, 20(2):240-249.
- 8. Xu Z, Joshi N, Agarwal A, et al. Knocking down nucleolin expr-ession in gliomas inhibits tumor growth and induces cell cycle arrest[J]. J Neurooncol, 2012, 108(1):59-67.
- 9. 王慷慨, 肖獻忠. 核仁素在細胞增殖與細胞凋亡中的作用[J]. 中南大學學報:醫(yī)學版, 2004, 29(6):707-710.
- 10. Peng L, Liang J, Wang H, et al. High levels of nucleolar expression of nucleolin are associated with better prognosis in patients with stageⅡpancreatic ductal adenocarcinoma[J]. Clin Cancer Res, 2010, 16(14):3734-3742.
- 11. 蒙國照, 肖勝軍, 曾思恩, 等. 細胞表面核仁素表達下調抑制肝癌細胞生長[J]. 中華腫瘤學雜志, 2011, 33(1):23-27.
- 12. 田曉彩, 劉先領, 胡春宏. 核仁素表達下調對阿霉素所致乳腺癌細胞增殖抑制和凋亡的影響[J]. 中華腫瘤雜志, 2010, 32(4):271-272.
- 13. Huang Y, Shi H, Zhou H, et al. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin[J]. Blood, 2006, 107(9):3564-3571.
- 14. Christian S, Pilch J, Akerman ME, et al. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels[J]. J Cell Biol, 2003, 163(4):871-878.
- 15. Reyes-Reyes EM, Akiyama SK. Cell surface nucleolin is a signal transducing P-selectin binding protein for human colon carcin cells[J]. Exp Cell Res, 2008, 314(11-12):2212-2223.
- 16. Turck N, Lefebvre O, Gross I, et al. Effect of laminin-1 on inte-stinal cell differentiation involves inhibition of nuclear nucleolin[J]. J Cell Physiol, 2006, 206(2):545-555.
- 17. Harms G, Kraft R, Grelle G, et al. Identification of nucleolin as a new L-selectin ligand[J]. Biochem J, 2001, 360(Pt 3):531-538.
- 18. Krust B, El Khoury D, Nondier I, et al. Targeting surface nucle-olin with multivalent HB-19 and related Nucant pseudopeptides results in distinct inhibitory mechanisms depending on the malignanttumor cell type[J]. BMC Cancer, 2011, 11:333.
- 19. Joo EJ, Yang H, Park Y, et al. Induction of nucleolin translocation by acharan sulfate in A549 human lung adenocarcinoma[J]. Cell Biochem, 2010, 110(5):1272-1278.
- 20. Qu WS, Tian DS, Guo ZB, et al. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the assoc-iated secondary damage in rats after spinal cord injury[J]. J Neur-oinflammation, 2012, 9:178.
- 21. 王曉艷, 沈守榮, 劉芬結, 等. 結腸癌中NGX6抑制EGFR/K-ras/JNK/c-Jun/cyclin D1信號通路的研究[J]. 生物化學與生物物理進展, 2008, 35(5):570-576.
- 22. Chen CH, Wang SW, Chen CW, et al. MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endom-etrial cancer[J]. Gynecol Oncol, 2013, 128(3):560-567.
- 23. Kobayashi K, Hagiwara K. Epidermal growth factor receptor(EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer(NSCLC)[J]. Target Oncol, 2013, 8(1):27-33.
- 24. Li C, Zhang X, Cheng L, et al. RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice[J]. Cancer Gene Ther, 2013, 20(2):101-108.
- 25. Heuckmann JM, Rauh D, Thomas RK. Epidermal growth factor receptor(EGFR) signaling and covalent EGFR inhibition in lung cancer[J]. J Clin Oncol, 2012, 30(27):3417-3420.
- 26. Yang W, Xia Y, Cao Y, et al. EGFR-induced and PKCε monou-biquitylation-dependent NF-κB activation upregulates PKM2 expression and promotes tumorigenesis[J]. Mol Cell, 2012, 48(5):771-784.
- 27. , 286(51):43816-43829.