SV40大T抗原在人脑肿瘤中的表达

目的　检测 Ｓ Ｖ４０ 早期区域基因编码产物大 Ｔ 抗原（ Ｔａｇ）在人脑肿瘤中的表达，探讨 Ｓ Ｖ４０ 与人脑肿瘤发生的病因学关系。方法　采用免疫共沉淀、银染色及 Ｗｅｓｔｅｒｎ印迹检测 ６５ 例人脑肿瘤组织、８ 例正常人脑组织及 ２ 株人脑胶质瘤细胞系中 Ｔａｇ 的表达。结果　 Ｔａｇ 在 ８ 例室管膜瘤、２ 例脉络丛乳头状瘤及 ２ 株人脑胶质瘤细胞系中全部表达；垂体腺瘤 Ｔａｇ 阳性率为 ９０％ （９／１０），星形胶质细胞瘤７３％ （１１／１５），脑 膜瘤 ７０％ （７／１０），多形性 胶质母细胞 瘤５０％ （４／８），髓母细胞瘤 ３３％ （２／６）；５ 例少枝胶质细胞瘤、１例松果体瘤及 ８ 例正常人脑组织无 Ｔａｇ 表达。结论　 Ｓ Ｖ４０感染与人脑肿瘤的发生有一定关系。     

猴病毒40是脑肿瘤发生的重要机制

第四军医大学西京医院神经外科研究所 ,近日完成的一项国家自然科学基金资助项目证实 ,猴病毒４０是致人脑肿瘤发生的一个重要机制。为探讨猴病毒４０早期区域基因编码产物大Ｔ抗原的表达及抑癌蛋白ｐ５３、ｐＲｂ的相互作用在人脑肿瘤发生发展中的意义。该所研究人员采用免疫共沉淀结合银染色及Ｗｅｓｔ ｅｒｎ印迹法检测６５例人脑肿瘤及８例正常人脑组织中大Ｔ抗原的表达 ,并对１８例和１５例大Ｔ抗原阳性瘤组织分别检测大Ｔ抗原 -ｐ５３和大Ｔ抗原 -ｐＲｂ复合物的形成。结果显示 ,猴病毒４０大Ｔ抗原在人脑肿瘤中广泛表达 ,阳性率为６…     

抑制LITAF基因对人脑胶质母细胞瘤U251细胞增殖、凋亡和放疗敏感度的影响

 目的 分析人脑胶质母细胞瘤组织中LITAF基因mRNA表达情况,并通过抑制人脑胶质母细胞瘤U251细胞中LITAF基因表达,观察其对U251细胞增殖、凋亡和放疗敏感度的影响。方法 分析TCGA数据库中人脑胶质母细胞瘤组织中LITAF基因mRNA表达;通过RNAi抑制U251细胞中LITAF基因表达,采用胸腺嘧啶核苷类似物（EDU）检测U251细胞增殖变化,流式细胞仪分析U251细胞凋亡的变化,克隆形成实验和流式细胞分析U251细胞放疗敏感度的变化。 结果 TCGA数据库分析结果显示人脑胶质母细胞瘤组织LITAF表达显著高于正常脑组织;抑制LITAF表达后,U251细胞的增殖和凋亡未见明显变化,但在电离辐射后,LITAF抑制组U251细胞凋亡显著低于对照组,克隆形成显著高于对照组,对放疗敏感度减弱。结论 LITAF基因高表达于人脑胶质母细胞瘤组织,抑制人脑胶质母细胞瘤U251细胞中LITAF基因表达不影响细胞的增殖和凋亡,但显著降低细胞的放疗敏感度。     

RANKL、RANK蛋白在胶质母细胞瘤组织中的表达及临床意义

目的:分析RANKL、RANK蛋白在胶质母细胞瘤组织中的表达及临床意义。方法:收集2017年10月至2019年10月于我科行手术治疗的21例胶质母细胞瘤患者的临床资料，用蛋白印迹试验检测肿瘤中心组织、瘤周组织、皮层造瘘脑组织中RANKL、RANK表达情况，并对其进行统计学分析。结果:肿瘤中心组织RANKL表达高于瘤周组织，有统计学差异(P=0.032)；瘤周组织高于皮层造瘘脑组织，有统计学差异(P=0.024)。瘤周组织RANK表达明显高于肿瘤中心组织，有统计学差异(P=0.006)；肿瘤中心组织高于皮层造瘘脑组织，有统计学差异(P=0.028)。结论:肿瘤中心组织中RANKL表达高于瘤周组织、脑组织，而瘤周组织中RANK明显高于肿瘤中心组织、肿瘤中心组织高于脑组织，我们认为RANKL/RANK通路可能在胶质母细胞瘤侵袭过程中起重要作用，有待后续进一步试验。     

胶质瘤中MKK7与c-Jun磷酸化的表达及其相关性

目的 探讨胶质瘤中MKK7和c-Jun磷酸化（p-c-Jun）的表达及意义，分析两者表达的相关性。方法 选取弥漫型星形细胞瘤（15例）、少突胶质细胞瘤（5例）、间变性星形细胞瘤（11例）、间变性少突胶质细胞瘤（8例）、胶质母细胞瘤（53例）及其瘤旁正常脑组织（25例）共117例，采用免疫组织化学法检测MKK7、c-Jun及p-c-Jun的表达。体外培养神经胶质瘤细胞株U87，用脂质体转染MKK4-siRNA、MKK7-siRNA和对照siRNA，48 h后Western blot检测MKK7、c-Jun及p-c-Jun的表达水平。结果 胶质母细胞瘤中p-c-Jun及MKK7的表达均明显高于其他组织学类型胶质瘤及胶质母细胞瘤瘤旁正常脑组织中的表达（P=0.000, P=0.000）。随着胶质瘤WHO分级的升高，p-c-Jun及MKK7的表达增高，且与WHO分级呈明显正相关（r=0.494, P=0.000; r=0.606, P=0.000）。胶质瘤及胶质母细胞瘤瘤旁正常脑组织中MKK7与p-c-Jun的表达存在正相关关系（r=0.387, P=0.000）。沉默神经胶质瘤细胞株U87 MKK7表达抑制了c-Jun磷酸化水平。结论 MKK7可以通过调控JNK/c-Jun活性进而促进胶质母细胞瘤的发生。     

胶质母细胞瘤中基质金属蛋白酶组织抑制物1、基质金属蛋白酶组织抑制物2的表达及与微血管密度的关系

目的 探讨胶质母细胞瘤中基质金属蛋白酶组织抑制物1(TIMP1)、基质金属蛋白酶组织抑制物2(TIMP2)的表达及与微血管密度(MVD)的关系.方法 收集42例接受手术治疗的胶质母细胞瘤患者的胶质母细胞瘤组织和周围正常组织.采用蛋白质印迹法检测两种组织中TIMP1、TIMP2的表达情况,采用免疫组化两步法检测两种组织的MVD.比较胶质母细胞瘤组织和周围正常组织中TIMP1、TIMP2的相对表达量及MVD值,比较不同组织学分级胶质母细胞瘤组织中TIMP1、TIMP2的相对表达量及MVD值,采用Pearson相关分析法分析胶质母细胞瘤组织中TIMP1、TIMP2表达与MVD的相关性.结果 胶质母细胞瘤组织中TIMP1、TIMP2的相对表达量均明显低于周围正常组织,MVD值明显高于周围正常组织,差异均有统计学意义(P﹤0.01).Ⅳ级胶质母细胞瘤组织中TIMP1、TIMP2的相对表达量均明显低于Ⅲ级胶质母细胞瘤组织,MVD值明显高于Ⅲ级胶质母细胞瘤组织,差异均有统计学意义(P﹤0.01).胶质母细胞瘤组织中TIMP1、TIMP2的表达均与MVD呈负相关(r=-0.796、-0.815,P﹤0.01).结论 胶质母细胞瘤组织中TIMP1、TIMP2的表达水平明显低于周围正常组织,MVD值明显高于周围正常组织,且恶性程度越高,TIMP1和TIMP2的表达水平越低,MVD值越高,TIMP1、TIMP2的表达均与MVD值呈负相关.     

BMP4在胶质母细胞瘤的多药耐药中的作用及机制研究

背景与目的：近年来的一系列实验证实,骨形成发生蛋白4（bone morphogenetic proteins 4,BMP41在体内外可以抑制肿瘤的生长,但其机制还不清楚。本研究旨在探讨BMP4在胶质母细胞瘤多药耐药中的作用及机制。方法：检测人脑胶质母细胞瘤和正常脑组织标本中BMPd的表达量：构建多药耐药细胞株并进行鉴定．检测在多药耐药细胞株和正常胶质母细胞瘤细胞株内BMP4的表达量：通过在多药耐药细胞株中高表达BMP4．检测BMP4逆转多药耐药的可能性：通过检测高表达BMP4后耐药相关基因的表达变化．初步筛选出BMPd调节胶质母细胞瘤多药耐药的可能机制。结果：在胶质母细胞瘤内,BMP4表达量降低：多药耐药细胞株构建成功．且与对照组相比,多药耐药细胞株的BMP4表达量明显降低,高表达BMP4可以逆转多药耐药：高表达BMP4后,多药耐药相关的基因中,BCL-2和GDNF表达量明显降低。结论：BMP4可以逆转胶质母细胞瘤多药耐药．其可能机制是通过调节BCL-2和GDNF的表达．     

DNMT1和p27蛋白在原发性与继发性胶质母细胞瘤中的表达及相关性

目的 探讨原发性胶质母细胞瘤和继发性胶质母细胞瘤中DNA甲基转移酶1（DNMT1）蛋白及p27蛋白的表达及相关性。方法 收集2000年1月1日至2012年12月31日经手术切除胶质母细胞瘤患者组织蜡块标本64例（原发胶质母细胞瘤32例,继发性胶质母细胞瘤32例）作为研究对象。检测64例胶质母细胞瘤标本和13例正常脑组织中DNMT1蛋白及p27蛋白的表达情况。结果 在正常脑组织中,DNMT1蛋白不表达,而在原发性和继发性胶质母细胞瘤中的阳性表达率分别为59.4%和81.3%。在正常脑组织中,p27蛋白的阳性表达率为100.0%,高于其在原发性和继发性胶质母细胞瘤中的50.0%和25.0%（P<0.05）。DNMT1 蛋白及p27蛋白在原发性和继发性胶质母细胞瘤中的表达差异存在统计学意义 （P<0.05）,但两者表达无相关性（r=0.41,P>0.05）。结论 DNMT1蛋白及p27蛋白在原发性和继发性胶质母细胞瘤中的表达存在差异,联合检测肿瘤标本中两者的表达情况有助于判断不同类型胶质母细胞瘤。     

酪氨酸激酶受体通路相关基因在原发胶质母细胞瘤中的表达及其意义

背景与目的:胶质母细胞瘤是颅内最常见的肿瘤之一,其发病率和死亡率均较高,但我们对其分子生物学机制仍了解甚少.本研究应用低密度表达谱芯片检测人脑原发胶质母细胞瘤组织中酪氨酸激酶受体通路相关基因的表达情况,进一步分析其表达变化的意义.方法:使用TaqMan低密度表达芯片技术检测26个酪氨酸激酶受体通路相关基因在10例原发胶质母细胞瘤及9例正常脑组织(脑外伤减压术中所取大脑组织)并通过统计学分析其在胶质母细胞瘤和正常脑组织中的表达差异.结果:在正常脑组织中,丝裂原活化蛋白激酶(MAPK)系统的两个基因MAP2K1及MAP2K4的Ct值分别为1.6±1.7和2.2±2.1,而在原发胶质母细胞瘤中的Ct值分别为3.9±1.5和5.0±2.0,其与正常脑组织的Ct差值分别为-2.3和-2.8(P<0.05).结论:MAP2K1和MAP2K4基因在原发胶质母细胞瘤中的表达明显下调;酪氨酸激酶受体通路相关基因中MAPK系统基因的表达差异可能与原发胶质母细胞瘤的发生、发展密切相关.     

TRAIL受体在胶质母细胞瘤中的表达及意义

目的:研究TRAIL受体(TRAIL receptor,TRAILR)在胶质母细胞瘤中的表达,探讨其临床意义.方法:联合采用免疫组化和原位杂交方法检测胶质母细胞瘤及正常脑组织中TRAILR的表达.结果:22例胶质母细胞瘤均大量表达死亡受体(Death receptor,DR)DR4和DR5,9例(40.9%)表达诱骗受体(Decoy receptor,DcR)DcR1,5例(22.7%)表达DcR2,而20例正常脑组织普遍表达DcR,8例(40.0%)表达DR4,6例(30.0%)表达DR5.胶质母细胞瘤组织中DR的高表达以及DcR的低表达不同于正常脑组织中DR的低表达及DcR的高表达,两者间差异有显著性(P＜0.01).原位杂交显示,22例胶质母细胞瘤组织分别有19例(864%)DcR1和17例(77.3%)DcR2在mRNA水平呈阳性表达,DcR在转录水平的表达明显高于翻译水平(P＜0.01).结论:胶质母细胞瘤中普遍存在DR的高表达和DcR的低表达,DcR在胶质母细胞瘤中限制性表达的调控位于转录后水平.这可能为胶质母细胞瘤的凋亡诱导治疗提供新的靶点和新的策略.     

Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors

BACKGROUND: The presence of simian virus 40 (SV40) in human brain tumors remains a controversial issue. Even if SV40 does exist in brain tumors, the questions of whether it is associated with brain tumorigenesis and by what mechanisms are unknown. METHODS: SV40 large tumor antigen (Tag) was investigated by immunoprecipitation, silver staining, and Western blot analysis in 65 brain tumor cases and 8 cases of normal brain tissue. Tag-p53 and Tag-pRb complexes were screened by immunoprecipitation and Western blot analysis in 18 and 15 Tag positive tumor tissues, respectively. RESULTS: Tag was found in all 8 cases of ependymoma and 2 cases of choroid plexus papilloma, 90% of pituitary adenoma cases (9 of 10), 73% of astrocytoma cases (11 of 15), 70% of meningioma cases (7 of 10), 50% of glioblastoma multiforme cases (4 of 8), and 33% of medulloblastoma cases (2 of 6). Five oligodendroglioma cases, 1 pineocytoma case, and 8 cases of normal brain tissue were negative for Tag. The Tag-p53 complex was detected in all 18 Tag positive tumors tested and the Tag-pRb complex was detected in all 15 Tag positive tumors tested. CONCLUSIONS: SV40 Tag not only is expressed in brain tumors; it also can form specific complexes with tumor suppressors p53 and pRb. SV40 is correlated with brain tumorigenesis. The inactivation of p53 and pRb due to the formation of Tag-p53 and Tag-pRb complexes possibly is a significant mechanism in the etiopathogenesis of brain tumors.     

EXPRESSION OF SV40 Tag AND FORMATION Tag-p53 AND Tag-Rb COMPLEXES IN CHINESE BRAIN TUMORS

Simian virus 40 (SV40), one type of polyomavirus, is able to transform different species including human normal cells to the neoplastic phenotype cell. The biological plausibility of SV40 as a tumorigenic agent has been extensively demonstrated. SV40 is tumorigenic in rodents and can immortalize human epithelial cell lines in vitro. It is also understood that SV40 large tumor antigen (Tag) interferes with p53 and Rb gene functions, and it may induce chromosomal instability. Furthermore, th…     

人脑胶质组织中SV40大T抗原表达及p53形成特异性复合物

目的 探讨SV40早期区域基因编码产物大T抗原（Tag）表达及与抑癌蛋白p53的相互作用在人脑胶质瘤发生发展中的意义。方法 采用免疫组织化学方法检测89例人脑胶质瘤组织和11例正常人脑组织中Tag的表达,并对Tag表达阳性肿瘤组织进行免疫共沉淀和Western blot表达阳性33例（阳性率37．1％）,Tag表达水平与胶质瘤病理分级呈显著正相关（pearson列联系数＝0．72,P＜0．01）;33例Tag表达阳性瘤组织中均发现Tag表达全部阴性。结果 SV40感染与人脑胶质瘤病因学密切相关,Tag可能是SV40在胶质瘤发生发展中起作用的重要因素;Tag可能是SV40在胶质瘤发生发展中起作用的重要因素：Tag与p53可形成特异性复合物,Tag-p53特异性复合物的形成导致p53失活,可能是人脑胶质癌发生发展的一个重要机理。     

Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors

BACKGROUND: Many studies found only a small fragment of the large T-antigen coding sequences in human tumors, raising doubts on authenticity of SV40 sequences detected in these samples. METHODS: Five different regions of SV40 DNA were investigated in 106 fresh human tumor biopsies (25 brain, 69 bone, 12 Wilms' tumors), 71 tumor-derived cell cultures (38 from brain and 33 from bone tumors) and normal tissues (5 fresh bone biopsies and 38 buffy coats) by polymerase chain reaction (PCR) techniques and filter hybridization with specific oligoprobes. Expression of SV40 Tag sequences was analyzed in human tumor specimens by RT-PCR. RESULTS: SV40 large T-antigen sequences were detected at high prevalence, in human biopsies of primary brain (37-44%) and bone (21-37%) tumors, in cell cultures derived from brain (30-54%) and bone (53-80%) tumors. SV40 Tag sequences were detected in 29% of buffy coats of blood donors. However, only four brain tumor cell lines showed all the five regions of the SV40 genome investigated. Expression of SV40 Tag sequences was found in 11 of 27 (41%) human tumor samples. DNA sequence analysis indicated that the PCR-amplified products belong to the SV40 wild type. Polymerase chain reaction products of Tag middle portion from 20 of 78 (26%) samples showed a 97% homology with telomeric sequences of human chromosomes 10 and 11. CONCLUSIONS: Authentic SV40 sequences were detected in human samples. The expression of SV40 Tag sequences indicates that SV40 could play a role, as a cofactor, in the onset/progression of specific human cancers. The inability to detect some regions of the virus genome may suggest that those regions are not required for tumor persistence or growth and have been lost or, alternatively, may be the result of assay conditions that were unable to PCR-amplify those regions in the tumors.     

SV40 BKV及JCV在人脑肿瘤中的表达

目的:探讨多瘤病毒SV40、BKV、JCV与人脑肿瘤发生之间的关系.方法:采用聚合酶链式反应(PCR)技术,对脑星形细胞瘤23例,少突胶质细胞瘤19例,室管膜瘤18例,脉络丛乳头状瘤12例,脑膜瘤11例及正常脑组织12例进行了三种病毒的检测.结果:SV40、BKV和JCV在脑肿瘤组织的阳性率分别为56.6%(47例)、53.0%(44例)和14.5%(12例);在正常脑组织中阳性率分别为8.3%(1例)、8.3%(1例)和16.7%(2例).SV40在脑肿瘤组织中阳性率显著高于正常脑组织(P＜0.01),所检测的五种脑肿瘤与正常组织相比具有显著性差异(P＜0.05);BKV在脑肿瘤组织中阳性率显著高于正常脑组织(P＜0.01),所检测的五种脑肿瘤与正常组织相比具有显著性差异(P＜0.05);SV40与BKV在脑肿瘤中的阳性率具有相关性(关联系数=0.56).JCV在肿瘤组织与正常组织间无显著性差异.结论:SV40及BKV参与脑肿瘤的发生.     

胶质瘤组织中SV40Tag Rb和IRS-1蛋白的表达及其与胶质瘤发生发展的关系

目的 探讨SV40Tag、Rb和IRS-1在胶质瘤发生发展过程中的关系和作用.方法 构建布有人脑胶质瘤和脑膜瘤临床标本为主体、配有实验性胶质瘤、正常人或鼠脑等相关组织等118个阵列的组织芯片,采用免疫组织化学和免疫荧光共聚焦技术检测SV40Tag、Rb和IRS-1的表达及SV40Tag与Rb、SV40Tag与IRS-1的联合表达.结果 SV40Tag、Rb和IRS-1在胶质瘤和脑膜瘤中均有表达,82例胶质瘤的阳性表达率分别为65.9%、64.6%和48.8%.正常人脑组织仅有Rb和IRS-1表达,而未见SV40Tag表达.SV40Tag和IRS-1的阳性表达率与病理分级呈正相关(P<0.05),Rb蛋白的阳性表达率与病理分级呈负相关(P<0.05).在82例胶质瘤中,SV40Tag与Rb、SV40Tag与IRS-1联合表达阳性率分别为51.2%和40.2%.结论 外源性SV40Tag随SV40病毒侵入机体,与Rb抑癌基因形成复合物使其抑癌功能丧失,同时诱导信号通路中重要成员IRS-1活化,从而促进细胞恶性变化,可能是脑胶质瘤发生发展的重要原因之一.     

Investigation of human brain tumors for the presence of polyomavirus genome sequences by two independent laboratories

JC virus (JCV), BK virus (BKV) and simian virus 40 (SV40) may be associated with human brain tumors. These polyomaviruses have been shown to induce brain tumors in experimentally infected animals. Several studies have found polyomavirus genomic sequences in human brain tumor tissues by using polymerase chain reaction (PCR), while others have not. Inconsistencies in previous findings may be due in part to small sample sizes and differences in underlying patient populations, laboratory techniques and quality control measures. To assess the role of polyomaviruses in human brain tumors and address inconsistencies of previous reports, we investigated the prevalence of viral sequences in a series of 225 brain tumor tissue specimens in 2 independent laboratories. PCR followed by Southern hybridization was performed at the National Institute of Neurological Disorders and Stroke (NINDS). Real-time quantitative PCR was performed on the same tissues at Johns Hopkins University (JHU). Only those tumors with amplifiable DNA were tested further for polyomavirus sequences. Positive and negative control tissues were included, and all specimens were masked. Amplifiable DNA was detected in 225/225 (100%) tumors at NINDS, 9 (4%) of which contained polyomavirus sequences (3 JCV-positive, 3 BKV-positive and 3 SV40-positive). The JHU laboratory amplified DNA from 165/225 (73%) tumors, of which 1 tumor tested positive (for SV40). No tumors tested positive in both laboratories. Results for masked quality control tissues were concordant between laboratories. Nucleotide sequences for JCV, BKV and SV40 are rarely present in a large series of adult and pediatric brain tumors.     

Association between SV40 and non-Hodgkin's lymphoma

Millions of people worldwide were inadvertently exposed to live simian virus 40 (SV40) between 1955 and 1963 through immunization with SV40-contaminated polio vaccines. Although the prevalence of SV40 infections in humans is not known, numerous studies suggest that SV40 is a pathogen resident in the human population today. SV40 is a potent DNA tumor virus that is known to induce primary brain cancers, bone cancers, mesotheliomas, and lymphomas in laboratory animals. SV40 oncogenesis is mediated by the viral large tumor antigen (T-ag), which inactivates the tumor suppressor proteins p53 and pRb. During the last decade, independent studies using different molecular biology techniques have shown the presence of SV40 DNA, T-ag, or other viral markers in primary human brain and bone cancers and malignant mesotheliomas. Evidence suggests that there may be geographic differences in the frequency of these virus-positive tumors. Recent large independent controlled studies have shown that SV40 T-ag DNA is significantly associated with human non-Hodgkin's lymphoma (NHL). In our study, we analyzed systemic NHL from 76 HIV-1-positive and 78 HIV-1-negative patients, and nonmalignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumors; 54 colon and breast carcinoma samples served as cancer controls. We used polymerase chain reaction (PCR) followed by Southern blot hybridization and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. SV40-specific DNA sequences were detected in 64 (42%) of 154 NHL, none of 186 nonmalignant lymphoid samples, and none of 54 control cancers. For NHL from HIV-1-positive patients, 33% contained SV40 DNA and 39% Epstein Barr virus (EBV) DNA, whereas NHLs from HIV-1-negative patients were 50% positive for SV40 and 15% positive for EBV. Few tumors were positive for both SV40 and EBV. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B cell and follicular-type lymphomas. We conclude that SV40 is significantly associated with some types of NHL and that lymphomas should be added to the types of human cancers associated with SV40.     

Involvement of insulin-like growth factor-insulin receptor signal pathway in the transgenic mouse model of medulloblastoma

A transgenic mouse model expressing Simian virus 40 T-antigen (SV40Tag) under the control of a tetracycline system was generated. In this model, a cerebellar tumor was developed after doxycycline hydrochloride treatment. Real time-polymerase chain reaction and immunohistochemistry results indicated that the SV40Tag gene was expressed in the tumor. Pathological analysis showed that the tumor belonged to medulloblastoma. Further molecular characterization of the tumor demonstrated that the insulin-like growth factor (IGF) signaling pathway was activated. We also found that the SV40Tag could bind and translocate insulin receptor substrate 1 into the nucleus in primary cultured tumor cells. The interaction between the IGF pathway and SV40Tag may contribute to the process of malignant transformation in medulloblastoma. This transgenic animal model provides an important tool for studies on the signal pathways involved in the preneoplastic process in medulloblastoma and could help to identify therapeutic targets for brain tumors. ( Cancer Sci 2008; 99: 234–240)