人脑胶质瘤中常见的原癌基因和抑癌基因在临床病理中的意义
作者：刘芳 徐庆中
单位：首都医科大学附属宣武医院病理科 100053
关键词：
诊断病理学杂志000126分类号：R730.1 文献标识码：A
文章编号：1007-8096(2000)01-0064-03 原癌基因过度表达和抑癌基因失活是脑肿瘤发生、发展的重要原因，在国内外有诸多文献论述，下面就人脑胶质瘤中常见的原癌基因、生长因子和抑癌基因的改变及其临床病理意义进行论述。
1原癌基因(oncogene)和生长因子
1.1C-erbB-1基因C-erbB-1定位于染色体7q上，它的表达产物是表皮生长因子受体(EGFR)，EGFR是一种细胞膜受体，分子量170KD，与配体表皮生长因子(EGF)、转化生长因子α(TGFα)结合后激活络氨酸激酶，通过传递信号参与调节细胞的增殖、分化。人胶质瘤中最常扩增的是C-erbB-1基因，在50%以上的人恶性胶质细胞瘤(HMGs)中过度表达和扩增，2/3C-erbB-1基因扩增伴基因重排，导致基因结构改变。最常见的改变为外显子2～7的框架内缺失，形成细胞外功能区缺失的δ(delta)EGFR[1]，其转录产物缺乏激素结合区域而持续磷酸化，产生持续生长刺激信号，该络氨酸蛋白磷酸化的上调作用加速非肿瘤增生状态的星形细胞的增殖分裂，导致细胞癌变。EGFR过度表达与脑星形细胞瘤病理分级有潜在关系，在高级别星形细胞瘤(WHOⅢ—Ⅳ级)中EGFR过度表达率显著高于低级别肿瘤，是一种能反映脑星形细胞增殖活性的生物学指标。儿童胶质瘤中C-erbB-1扩增较少见，这与儿童胶质瘤普遍组织学级别较低相一致。
, 百拇医药
1.2血小板源性生长因子(platelet-derivedgrowthfactor，PDGF)PDGF是由A、B多肽链通过二硫键连接的30KD蛋白二聚体(A、B多肽链约有60%的氨基酸序列相似)，它的三种亚型(AA、AB、BB)分别与两种结构相似但亲和力及特异性均不同的PDCF受体结合：α和β受体，PDGFα受体和PDGFβ受体分别与AA、AB、BB型和BB型PDGF有较高亲和力。体内胶质瘤存在PDGF自分泌环，PDGF与细胞表面的PDGF受(全文见PDF)
参考文献：
[1]O’ Rourke DM, Zhang X, Greene MI.The neu ectodomain inhibits en-hanced in vivo tumorigenicity conferred by a mutant epidermal growth fac-tor receptor commonly found in human gliomas(Meeting abstract).Proc Annu Meet Am Assoc Cancer Res,1997,38:A1553
, 百拇医药
[2]Westermark B,Nister M.Platelet-derived growht factor in human glima,Gila,1995,15:257-63
[3]Kuratsu J,Sato K,Saitohy,et al.The mechanism of growth-regulation of glioms cells by trapidil.J Neurooncol,1995,23:201-6
[4]Nakasu S,Nakajima M,Nioka H,et al.bcl-2 protein expression in tumors of the central nervous system. Acta Neuropathol(Ber),1994,88:520-6
[5]Krajewski S, Krajewska M,Ehrman J,et al.Immunohistochemical analysis of Bcl-2,Bcl-X,Mcl-1,and Bax in tumors of central and peripheral ner-vous system origin.Am J Pathol,1997,150:805-14
, 百拇医药
[6]Das R,Reddy EP,Chatterjee D,et al.Identification of a novel Bcl-2 relat-ed gene,BRAG-1,in human glioma.Oncogene,1996,12:947-51
[7]Koochekpour S, Maidment SL.Met and hepatocyte growth factor/scatter factor expression in human gliomas.Cancer Res,1997,57:5391-8
[8]Takahashi JA,Fukumoto M,Igarashi K, et al.correlation of basic fibrob-last growth factor expression levels with the degree of malignancy and vas-cularity in human gilomas.J Neurosurg,1992,76:792-8
, 百拇医药
[9]Stefanik DF,Rizkalla LR,Soi A.acidic and basic fibroblast growth factors are present in glioblastoma multiforme.Cancer Res,1991,51:5760-5
[10]Stachowiak MK,Stachowiak EK,Maher PA,et al.Growth factor regula-tion of cell growth and proliferation in the nervous system.A new in-tracrine nuclear mecharism. Mol Neurobio, 1997,15:257-83
[11]Plate KH, Mennel HD.Vascular morphology and angiogenesis in glial tu-mors.Exp Toxicol Pathol,1995,47:89-94
, http://www.100md.com
[12]Wafik SE, Takashi T, WAF1, a potential mediator of p53 tumor suppres-sion. Cell,1993,75: 817-825
[13]Pykett MJ, Azzam E, Dahlberg W,et al.Differential p53, p21,mdm2 and Rb regulation in glioma cell lines that overexpress wild-type p53.Int J Oncol,1998,13:213-6
[14]Izumoto S,Hiraga S,Taki T. Homozygous deletions of p16INK4A/MTS1 and 915INK4B/MTS2 genes in glioma cells and primary glioma tissues.Caneer Lett, 1995,97:241-7
, 百拇医药
[15]Jung JM, Butler JM,Mccord BR.Increased levels of p21WAF1/Cip1 in human brain trump. Oncogene,1995,11:2021-8
[16]Maier D, Zhang Z, Taylor E,et al.Somatic deletion mapping on chromo-some 10 and sequence analysis of PIEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas.Oncogene,1998,16:3331-5
[17]Nakanura H, Yoshkids M, Tsulki H, et al.Identification of a human ho-molog of the Drosphila neuralized gene within the 10q25.1 malignant astrocytoma deletion region. Oncogene, 1998,16:1009-19
收稿日期：1999-02-01
修稿日期：1999-05-18, 百拇医药
单位：首都医科大学附属宣武医院病理科 100053
关键词：
诊断病理学杂志000126分类号：R730.1 文献标识码：A
文章编号：1007-8096(2000)01-0064-03 原癌基因过度表达和抑癌基因失活是脑肿瘤发生、发展的重要原因，在国内外有诸多文献论述，下面就人脑胶质瘤中常见的原癌基因、生长因子和抑癌基因的改变及其临床病理意义进行论述。
1原癌基因(oncogene)和生长因子
1.1C-erbB-1基因C-erbB-1定位于染色体7q上，它的表达产物是表皮生长因子受体(EGFR)，EGFR是一种细胞膜受体，分子量170KD，与配体表皮生长因子(EGF)、转化生长因子α(TGFα)结合后激活络氨酸激酶，通过传递信号参与调节细胞的增殖、分化。人胶质瘤中最常扩增的是C-erbB-1基因，在50%以上的人恶性胶质细胞瘤(HMGs)中过度表达和扩增，2/3C-erbB-1基因扩增伴基因重排，导致基因结构改变。最常见的改变为外显子2～7的框架内缺失，形成细胞外功能区缺失的δ(delta)EGFR[1]，其转录产物缺乏激素结合区域而持续磷酸化，产生持续生长刺激信号，该络氨酸蛋白磷酸化的上调作用加速非肿瘤增生状态的星形细胞的增殖分裂，导致细胞癌变。EGFR过度表达与脑星形细胞瘤病理分级有潜在关系，在高级别星形细胞瘤(WHOⅢ—Ⅳ级)中EGFR过度表达率显著高于低级别肿瘤，是一种能反映脑星形细胞增殖活性的生物学指标。儿童胶质瘤中C-erbB-1扩增较少见，这与儿童胶质瘤普遍组织学级别较低相一致。
, 百拇医药
1.2血小板源性生长因子(platelet-derivedgrowthfactor，PDGF)PDGF是由A、B多肽链通过二硫键连接的30KD蛋白二聚体(A、B多肽链约有60%的氨基酸序列相似)，它的三种亚型(AA、AB、BB)分别与两种结构相似但亲和力及特异性均不同的PDCF受体结合：α和β受体，PDGFα受体和PDGFβ受体分别与AA、AB、BB型和BB型PDGF有较高亲和力。体内胶质瘤存在PDGF自分泌环，PDGF与细胞表面的PDGF受(全文见PDF)
参考文献：
[1]O’ Rourke DM, Zhang X, Greene MI.The neu ectodomain inhibits en-hanced in vivo tumorigenicity conferred by a mutant epidermal growth fac-tor receptor commonly found in human gliomas(Meeting abstract).Proc Annu Meet Am Assoc Cancer Res,1997,38:A1553
, 百拇医药
[2]Westermark B,Nister M.Platelet-derived growht factor in human glima,Gila,1995,15:257-63
[3]Kuratsu J,Sato K,Saitohy,et al.The mechanism of growth-regulation of glioms cells by trapidil.J Neurooncol,1995,23:201-6
[4]Nakasu S,Nakajima M,Nioka H,et al.bcl-2 protein expression in tumors of the central nervous system. Acta Neuropathol(Ber),1994,88:520-6
[5]Krajewski S, Krajewska M,Ehrman J,et al.Immunohistochemical analysis of Bcl-2,Bcl-X,Mcl-1,and Bax in tumors of central and peripheral ner-vous system origin.Am J Pathol,1997,150:805-14
, 百拇医药
[6]Das R,Reddy EP,Chatterjee D,et al.Identification of a novel Bcl-2 relat-ed gene,BRAG-1,in human glioma.Oncogene,1996,12:947-51
[7]Koochekpour S, Maidment SL.Met and hepatocyte growth factor/scatter factor expression in human gliomas.Cancer Res,1997,57:5391-8
[8]Takahashi JA,Fukumoto M,Igarashi K, et al.correlation of basic fibrob-last growth factor expression levels with the degree of malignancy and vas-cularity in human gilomas.J Neurosurg,1992,76:792-8
, 百拇医药
[9]Stefanik DF,Rizkalla LR,Soi A.acidic and basic fibroblast growth factors are present in glioblastoma multiforme.Cancer Res,1991,51:5760-5
[10]Stachowiak MK,Stachowiak EK,Maher PA,et al.Growth factor regula-tion of cell growth and proliferation in the nervous system.A new in-tracrine nuclear mecharism. Mol Neurobio, 1997,15:257-83
[11]Plate KH, Mennel HD.Vascular morphology and angiogenesis in glial tu-mors.Exp Toxicol Pathol,1995,47:89-94
, http://www.100md.com
[12]Wafik SE, Takashi T, WAF1, a potential mediator of p53 tumor suppres-sion. Cell,1993,75: 817-825
[13]Pykett MJ, Azzam E, Dahlberg W,et al.Differential p53, p21,mdm2 and Rb regulation in glioma cell lines that overexpress wild-type p53.Int J Oncol,1998,13:213-6
[14]Izumoto S,Hiraga S,Taki T. Homozygous deletions of p16INK4A/MTS1 and 915INK4B/MTS2 genes in glioma cells and primary glioma tissues.Caneer Lett, 1995,97:241-7
, 百拇医药
[15]Jung JM, Butler JM,Mccord BR.Increased levels of p21WAF1/Cip1 in human brain trump. Oncogene,1995,11:2021-8
[16]Maier D, Zhang Z, Taylor E,et al.Somatic deletion mapping on chromo-some 10 and sequence analysis of PIEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas.Oncogene,1998,16:3331-5
[17]Nakanura H, Yoshkids M, Tsulki H, et al.Identification of a human ho-molog of the Drosphila neuralized gene within the 10q25.1 malignant astrocytoma deletion region. Oncogene, 1998,16:1009-19
收稿日期：1999-02-01
修稿日期：1999-05-18, 百拇医药