PTTG、bFGF、VEGF-C在大肠正常黏膜及大肠癌中的表达及意义

探讨垂体肿瘤转化基因（PTTG）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子-C（VEGF-C）在大肠癌中的表达及以上指标与大肠癌临床病理因素之间的关系。方法：采用RT-PCR技术检测20例大肠正常黏膜、80例大肠癌组织中PTTG mRNA,应用免疫组织化学法检测20例大肠正常黏膜、80例大肠癌组织中PTTG、bFGF、VEGF-C蛋白的表达。结果：大肠癌组织中PTTG、bFGF、VEGF-C的表达明显高于大肠正常黏膜组织,且与大肠癌浸润深度、淋巴结转移、Duke's分期呈正相关,PTTG、bFGF、VEGF-C在大肠癌中的表达有显著正相关性。结论：PTTG、bFGF、VEGF-C在大肠癌发生、发展、侵袭及转移过程中扮演着重要的角色,可作为判断大肠癌转移及预后的预测因素,且三者可能通过相互作用共同促进大肠癌的恶性进展。     

PTTG靶向siRNA表达载体构建及其沉默效率评价

目的：构建针对人脑胶质瘤细胞系U251的高效率沉默垂体瘤转化基因(PTTG)的小分子干扰RNA(siRNA)表达载体。 方法：合成特异性干扰PTTG 的siRNA片段,并与pGenesil2 载体连接,构建PTTG干扰载体（pGenesil2-PTTG siRNA）。利用脂质体将其转染U251细胞,分为正常细胞对照组、HK阴性对照组和3个siRNA干扰组（pGenesil2-PTTG siRNA1、pGenesil2-PTTG siRNA2和pGenesil2-PTTG siRNA3）,应用半定量逆转录聚合酶链式反应(RT-PCR)法和流式细胞术对转染后U251细胞中PTTG 的mRNA和蛋白表达水平进行分析。 结果：酶切证实PTTG-siRNA表达载体构建成功,插入片段测序结果与合成的siRNA结果一致;转染pGenesil2-PTTG siRNA后,3个干扰组的U251 细胞中PTTG基因和蛋白表达水平均较正常对照组显著降低（P<0.01）。 结论：成功构建了能高效率沉默PTTG 的RNAi表达载体;pGenesil2-PTTG siRNA高效地抑制了胶质瘤U251细胞中PTTG基因的表达。     

Expression of MMP14 in invasive pituitary adenomas: relationship to invasion and angiogenesis

Pituitary adenomas (PAs) are noncancerous tumors, and about 35% of those reported to be invasive have been classified as “invasive pituitary adenomas (IPAs)”. In clinical, operative complications, total resection failures, and high relapse rates result from invasive features during the therapeutic process. Invasive mechanism is a complex process, including metalloproteases, inhibitors and tumor microenvironment factors etc. Thus, studying invasive mechanism of PAs might contribute to understanding its biological behavior. In our research, three type tissue samples of human, pituitaries, PAs, IPAs, their mRNA expression of MMP1, MMP2, MMP9, MMP14 and MMP15 were measured using real-time PCR. MMP2 and MMP14 protein levels also were measured with immunohistochemistry in same samples. We confirmed that elevated matrix metalloproteinase-14 expression correlates with invasive characteristics of IPAs. To investigate molecular mechanism of how MMP14 contributes to invasiveness, an ATT20 cell was used in this study. After transient-transfection of the MMP14-shRNA expression vector into ATT20 cells, we observed that mRNA expression of PTTG, VEGF, and TGFβ was significantly suppressed in interference groups. Meanwhile, ATT20 cells in high concentration TIMP-1 environment exhibit reduced PTTG, VEGF, and TGFβ expression accompanied with the down-regulation of MMP14. Thus, we propose that MMP14 plays an important role in tumor invasion and angiogenesis and that a novel regulatory pathway for MMP14 may exist through VEGF and PTTG. In brief, MMP14 may be a target for therapeutic treatment.     

PTTG 在垂体腺瘤各亚型中的表达与分析

目的:研究PTTG与垂体瘤的各亚型的相关性.方法:用免疫组化方法检测92例垂体肿瘤病人PTTG.其中29例GH,20例PRL,10例ACTH,11例FSH/LH,9例TSH和13例无功能腺瘤.结果:PTTG在细胞质内显著表达,各亚型中GH型是表达最高,PRL腺瘤表达最低,各亚型的阳性表达率与PRL亚型阳性表达率对比均有统计学意义.结论:重体腺瘤不同垂体亚型中PTTG的表达阳性率及表达强度不同,PTTG检测,可为早期诊断垂体腺瘤( GH、PRL、ACTH、FSH/LH、TSH)亚型和无功能型提供参考.     

脑膜瘤组织中PTTG1、E2F3、EphA2蛋白水平与患者预后的关系研究

目的 探讨脑膜瘤组织中垂体肿瘤转化基因1(PTTG1)、E2F转录因子3(E2F3)和上皮细胞激酶(EphA2)蛋白水平与患者预后的关系.方法 选择65例脑膜瘤患者作为观察组,另取同期收治的63例脑膜瘤旁组织作为对照组,测定PTTG1、E2F3、EphA2蛋白在脑膜瘤组织和瘤旁组织中的表达水平,并分析其与患者临床病理特...     

PTTG与垂体腺瘤发生学

垂体瘤转化基因(PTTG)是近年来新发现的原癌基因,在正常垂体有限表达或不表达,在垂体腺瘤呈高水平表达。PTTG的C-末端脯氨酸富集区含有PXXP花簇,通过SH3中介的信号传导通路,刺激bFGF表达和细胞外分泌,导致体外细胞转化和体内实体肿瘤形成。PTTG还可通过激活c-myc基因转录,或编码一个封闭素样蛋白,抑制细胞分裂期染色单体分离,产生非整倍体变异,引起细胞转化和肿瘤形成。     

Upregulation of PTTG1 is associated with poor prognosis in prostate cancer

Pituitary tumor‐transforming gene 1 (PTTG1) is a regulator of chromosome stability. PTTG1 overexpression had been associated with tumor aggressiveness in several cancer types. To examine its prognostic utility in prostate cancer, a tissue microarray including 12 427 tumors with clinical and molecular data was analyzed by immunohistochemistry. PTTG1 immunostaining was largely absent in normal prostate epithelial cells. In cancers, staining was considered weak in 5.4%, moderate in 5.6% and strong in 0.8%. Strong staining was linked to advanced pT stage, high classical and quantitative Gleason grade, high Ki67‐labeling index (all P < 0.0001) and lymph node metastasis (P = 0.0083). The prognostic impact of PTTG1 expression was independent of established preoperative and postoperative prognostic features. Comparison with molecular features revealed that PTTG1 upregulation was associated with nine of 12 common genomic deletions (P < 0.05), p53 alterations and high androgen receptor levels (P < 0.001 each), but was unrelated to the TMPRSS2:ERG fusion status. In conclusion, these data identify PTTG1 as a strong and independent prognostic feature in prostate cancer. PTTG1 measurement, either alone or in combination with other biomarkers might be instrumental for determining prostate cancer aggressiveness.     

PTTG基因及Ki67抗原在胃癌组织中的表达及意义

目的　探讨PTTG基因和Ki6 7在胃癌发生、发展中的作用及二者的相关性。方法　采用免疫组织化学SP法检测了4 0例胃癌患者胃组织中PTTG基因和Ki6 7的表达情况。结果　PTTG基因和Ki6 7在胃癌组织中的阳性表达率分别为72 .5 %和95 % ,均与胃癌的病理组织学分级、临床分期及淋巴结转移有关(P<0 .0 5 ) ,而与组织学类型无关(P>0 .0 5 )。PTTG基因和Ki6 7表达强度呈显著正相关(P<0 .0 5 )。结论　PTTG基因和Ki6 7在胃癌的发生、发展中有协同作用,可作为反映胃癌生物学行为的指标。     

肝癌组织PTTG和VEGF的表达与肿瘤血管生成的关系及临床意义

目的 分析PTTG和VEGF在肝癌中的表达及其与肿瘤血管生成的关系。方法 采用免疫组化S-P法,检测原发性肝细胞性肝癌（HCC）50例、肝硬化30例、正常肝10例组织中PTTG、VEGF的表达.结果 PTTG、VEGF在原发性肝癌、肝硬化和正常肝组织中的表达差异有统计学意义（F=7.4,F=8.5,P〈0.01）。结论 PTTG、VEGF异常表达与肝癌肝硬化的发展密切相关,对肿瘤新生血管起关键作用,为肝癌的早期诊断提供了较为客观的参考指标。