SOCS-3 mRNA在胃癌组织及胃癌细胞系中的表达
摘要
自从1997年SOCS家族被发现以来,其功能日趋明了。SOCS蛋白与细胞因子受体结合发挥负性调节作用。SOCS蛋白通过促进蛋白酶体水解JAK/STAT途径的信号蛋白发挥负性调节作用,SOCS这样蛋白信号可能促进蛋白的退化。尽管SOCS可在体内通过抑制JAK2活性阻断LIF介导的STAT3活化,但体外实验显示SOCS-3和JAK亲和力极低,不能发挥抑制作用。这表明SOCS-3的负性调节作用还存在更复杂的机制。SOCS-3蛋白可能通过负调控细胞内信号通路抑制肺癌细胞增殖。在某些组织的肿瘤检测到SOCS-3表达下降,甚至缺失。
本文研究了人胃癌细胞mRNA中细胞因子信号转导负调控因子3(SOCS-3)的表达。提取人胃癌组织及SWWC细胞系细胞中的mRNA,应用RT-PCR法测定SOCS-3的表达。与正常胃组织相比较,本研究中所测定的10个人胃癌组织(p<0.05)及人胃癌细胞系SWWC (p<0.001)SOCS-3 mRNA的表达呈降低趋势。在人胃癌的发生、发展过程中SOCS-3基因发生显著变化。
Objective: To approach the expressions of suppressors ofcytokine signaling-3(SOCS-3) in gastric cancer tissue ofhuman and carcinoma cell line of stomach。
Methods:we determined the expressions of SOCS-3 in 10normal gastric tissues of human,10 gastric cancer tissues ofhuman and 10 carcinoma cell line of stomach SWWC by themethod of RT-PCR。
Result:comparisoning normal gastric tissue of human, theexpressions of SOCS-3 mRNA depressed in gastric cancertissue of human (p<0.05) and carcinoma cell line of stomachSWWC (p<0.001) in our study。
Conclusion: the gene of SOCS-3 diversities predominantlyand tends depression in development of gastric cancer。
本文研究了人胃癌细胞mRNA中细胞因子信号转导负调控因子3(SOCS-3)的表达。提取人胃癌组织及SWWC细胞系细胞中的mRNA,应用RT-PCR法测定SOCS-3的表达。与正常胃组织相比较,本研究中所测定的10个人胃癌组织(p<0.05)及人胃癌细胞系SWWC (p<0.001)SOCS-3 mRNA的表达呈降低趋势。在人胃癌的发生、发展过程中SOCS-3基因发生显著变化。
Objective: To approach the expressions of suppressors ofcytokine signaling-3(SOCS-3) in gastric cancer tissue ofhuman and carcinoma cell line of stomach。
Methods:we determined the expressions of SOCS-3 in 10normal gastric tissues of human,10 gastric cancer tissues ofhuman and 10 carcinoma cell line of stomach SWWC by themethod of RT-PCR。
Result:comparisoning normal gastric tissue of human, theexpressions of SOCS-3 mRNA depressed in gastric cancertissue of human (p<0.05) and carcinoma cell line of stomachSWWC (p<0.001) in our study。
Conclusion: the gene of SOCS-3 diversities predominantlyand tends depression in development of gastric cancer。
引文
1) 白莉 钱桂生 王关嵩 细胞因子信号转导负调控因子家族《生命的化学》2001 年 22 卷第 5 期 448-451。
2) Nicholson SE, Hilton DJ. The SOCS proteins: a new family of negative regulations of signal transctuction. J Leukoc Biol.1998;63:665.
3) Diamond P. Doran P, Brady HR et al. Suppressors of cytokine signaling (socs);putative modulators of cytokine bioactivity in health and disease. J Nephrol.2000;13:9.
4) Brender C, Nielsen M, Kaltoft K, et al. STAT3 mediatedconstitutive expression of SOCS-3 in cutaneous T-cell lymphoma[J]. Neoplasia.2001;97(4):1056-1062.
5) Biao He, Liang You et al. SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer. Proc Natl Acad Sci USA. 2003;100(24):14133-14138.
6) Hansen JA, Lindberg K, Hilton DJ et al. Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling preteins. Mol Endocrinol 1999;13:1832-1843.
7) Nicholson SE, De Souza D, Fabri LJ et al. Suppressor of cytokine signaling-3 preferentially binds to the SHP-2 binding site on the shared cytokine receptor subunit gp 130. Proc Natl Acad Sci USA 2000;97:6493-6498.
8) Danielle L. Krebs Douglas J. Hilton SOCS proteins: negative regulators of cytokine signaling Stem Cells 2001;19:378-387.
9) 余祖滨 闵家新等 SOCS-3 基因转染对人肺腺癌细胞株 A549增殖的影响 癌症 2004 年 23 卷第 9 期:1047-1051。
10) 田志刚 JAK/STAT 信号传导通路特异抑制物—SOCS 系统的发现及意义 中国免疫学杂志 2000 年第 16 卷:454-455。
11) Oliver Glm, Hirohide Yoshikawa, et al. SOCS-1,A negative regulator of cytokine signaling, Is frequently silenced by methylation in multiple myeloma Blood. 2003;101:2784-2788.
12) Ikuya Sakai, Kazuto Takeuchi, et al. Constitutive expression of SOCS-3 confers resistance to IFN-α in chronic myelogenous leukemia cells Blood,2002;100:2926-2931.
13) Brender C, Nielsen M, Kaltoft K, et al. STAT3 mediated constitutive expression of SOCS-3 in cutaneous Tcell lymphoma.Blood.2001;97:1056-1062.
14) Shen X, Hong F, Nguen V-A, Gao B.IL-10attenuares IFN -activated STAT-1 in the liver: involvement of SOCS-2 and SOCS-3.FEEBS Lett.2000;480:132-136.
15) Song MM, Shuai K. The suppressor of cytokine signalng(SOCS) 1 and SOCS-3 but not SOCS-2 proteins inhibit interferonmediated antiviral and antiprolferative activities. J Biol Chem.1998;273:35056-35062.
16) Ito S, Ansari P, Sakatsume M, et al. Interleukin-10 inhibits expression of both interferon-α and interferon-γ inducedgenes by suppressing tyrosine phosphorylation of STAT1.Blood.1999;93:1456-1463.
17) Frantsve J, Schwaller J,Sternberg DW, Kutok J, Gilliland DG. Socs-1 inhibits TEL/JAK2 mediated transformation of hematopoietic cells through inhibition of JAK2 kinase activity and induction of proteasome mediated degradation.2001;21: 3547–3557.
18) Carmen Gómez Guerrero, Oscar López Franco, et al. suppressors of cytokine signaling regulate Fc receptor signaling and cell activation during immune renal injury The Journal of Immunology.2004;172:6969-6977.
19) Kamizono S, Hanada T, Yasukawa H, Minoguchi S, Kato R, Minoguchi M, Hattori K, Hatakeyama S, Yada M, Morita S et al. The SOCS box of SOCS-1 accelerates ubiquitin dependent proteolysis of TEL/JAK2. 2001;276:12530–12538.
20) Aaronson DS, Horvath CMA. road map for those who do not know JAK/STAT. 2002;296: 1653–1655.
21) Hirohide Yoshikawa, Kenichi Matsubara, et al. SOCS-1,A negative regulator of the JAK/STAT pathway, is silencedby methylation in human hepatocellular carcinoma and shows growth suppression activity Nature Genetics.2001;28: 29-35.
2) Nicholson SE, Hilton DJ. The SOCS proteins: a new family of negative regulations of signal transctuction. J Leukoc Biol.1998;63:665.
3) Diamond P. Doran P, Brady HR et al. Suppressors of cytokine signaling (socs);putative modulators of cytokine bioactivity in health and disease. J Nephrol.2000;13:9.
4) Brender C, Nielsen M, Kaltoft K, et al. STAT3 mediatedconstitutive expression of SOCS-3 in cutaneous T-cell lymphoma[J]. Neoplasia.2001;97(4):1056-1062.
5) Biao He, Liang You et al. SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer. Proc Natl Acad Sci USA. 2003;100(24):14133-14138.
6) Hansen JA, Lindberg K, Hilton DJ et al. Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling preteins. Mol Endocrinol 1999;13:1832-1843.
7) Nicholson SE, De Souza D, Fabri LJ et al. Suppressor of cytokine signaling-3 preferentially binds to the SHP-2 binding site on the shared cytokine receptor subunit gp 130. Proc Natl Acad Sci USA 2000;97:6493-6498.
8) Danielle L. Krebs Douglas J. Hilton SOCS proteins: negative regulators of cytokine signaling Stem Cells 2001;19:378-387.
9) 余祖滨 闵家新等 SOCS-3 基因转染对人肺腺癌细胞株 A549增殖的影响 癌症 2004 年 23 卷第 9 期:1047-1051。
10) 田志刚 JAK/STAT 信号传导通路特异抑制物—SOCS 系统的发现及意义 中国免疫学杂志 2000 年第 16 卷:454-455。
11) Oliver Glm, Hirohide Yoshikawa, et al. SOCS-1,A negative regulator of cytokine signaling, Is frequently silenced by methylation in multiple myeloma Blood. 2003;101:2784-2788.
12) Ikuya Sakai, Kazuto Takeuchi, et al. Constitutive expression of SOCS-3 confers resistance to IFN-α in chronic myelogenous leukemia cells Blood,2002;100:2926-2931.
13) Brender C, Nielsen M, Kaltoft K, et al. STAT3 mediated constitutive expression of SOCS-3 in cutaneous Tcell lymphoma.Blood.2001;97:1056-1062.
14) Shen X, Hong F, Nguen V-A, Gao B.IL-10attenuares IFN -activated STAT-1 in the liver: involvement of SOCS-2 and SOCS-3.FEEBS Lett.2000;480:132-136.
15) Song MM, Shuai K. The suppressor of cytokine signalng(SOCS) 1 and SOCS-3 but not SOCS-2 proteins inhibit interferonmediated antiviral and antiprolferative activities. J Biol Chem.1998;273:35056-35062.
16) Ito S, Ansari P, Sakatsume M, et al. Interleukin-10 inhibits expression of both interferon-α and interferon-γ inducedgenes by suppressing tyrosine phosphorylation of STAT1.Blood.1999;93:1456-1463.
17) Frantsve J, Schwaller J,Sternberg DW, Kutok J, Gilliland DG. Socs-1 inhibits TEL/JAK2 mediated transformation of hematopoietic cells through inhibition of JAK2 kinase activity and induction of proteasome mediated degradation.2001;21: 3547–3557.
18) Carmen Gómez Guerrero, Oscar López Franco, et al. suppressors of cytokine signaling regulate Fc receptor signaling and cell activation during immune renal injury The Journal of Immunology.2004;172:6969-6977.
19) Kamizono S, Hanada T, Yasukawa H, Minoguchi S, Kato R, Minoguchi M, Hattori K, Hatakeyama S, Yada M, Morita S et al. The SOCS box of SOCS-1 accelerates ubiquitin dependent proteolysis of TEL/JAK2. 2001;276:12530–12538.
20) Aaronson DS, Horvath CMA. road map for those who do not know JAK/STAT. 2002;296: 1653–1655.
21) Hirohide Yoshikawa, Kenichi Matsubara, et al. SOCS-1,A negative regulator of the JAK/STAT pathway, is silencedby methylation in human hepatocellular carcinoma and shows growth suppression activity Nature Genetics.2001;28: 29-35.