基因转录与pre-mRNA剪接的偶联蛋白

真核基因的表达是一个复杂的过程,包括转录、pre-mRNA剪接、翻译等步骤。其中转录和pre-mRNA的剪接是基因表达中的两个重要环节,它们都要通过复杂的蛋白复合物来执行功能。目前研究发现这两个过程并不是绝对独立的,而是偶联在一起同时进行的。多种蛋白的偶联作用将二者联系在一起。RNA聚合酶Ⅱ、SKIP、SMN以及新近发现的人类P100蛋白不仅参与基因转录调节,同时它们在剪接加工中也具有相应的作用。     

WNT信号通路与肿瘤

WNT信号通路在肿瘤发生中有重要意义,它调节细胞生长、迁移和分化。由于它在众多人类肿瘤的发生中广泛活化,近年来这条通路在肿瘤研究方面受到很多关注。本文将介绍该通路与肿瘤发生的关系,以及目前该通路的研究在抗肿瘤治疗中的应用前景。     

DNA甲基化与基因转录抑制

DNA甲基化作为一种重要的表观遗传修饰,调节着机体许多生物学过程。DNA甲基化由DNA甲基转移酶催化 ,在多种调节因子的参与下,与组蛋白修饰相互作用,抑制基因转录,导致基因沉默。探讨DNA甲基化与基因转录抑制之间的关系,对许多人类疾病的研究具有重要意义。     

TGFβ信号通路与肿瘤

TGFβ影响细胞的增殖和分化 ,在肿瘤发生与进展、细胞外基质形成和免疫调节等过程中发挥重要作用。TGFβ通过胞膜上的受体和胞内 Sm ads家族向核内传递信号 ,调控靶基因。肿瘤中的 TGFβ信号通路异常有其多样性和复杂性。近年来 ,TGFβ信号通路的研究取得了突破性进展 ,本文综述了恶性肿瘤中的 TGFβ信号通路的异常。     

IL-6信号通路与肿瘤

IL-6(intedeukin-6)是迄今为止发现的功能最为广泛的细胞因子之一,参与调节免疫反应、血细胞的生成及多种细胞的增殖和分化.IL-6通过与其受体结合,继而活化胞内一系列信号蛋白分子,最终实现IL-6反应基因的表达.起初对IL-6的研究是将其作为一种炎性因子,后来又发现它与肿瘤的发生、发展及侵袭、转移密切相关.现对IL-6及其受体介导的信号通路及IL-6在肿瘤发生、发展中的作用及其机制作一简要综述.     

AP-1信号转导通路与肿瘤

近年来,AP-1信号转导通路与肿瘤的研究取得了突破性进展.血清因子、TPA及许多癌基因均能活化AP-1,促使细胞增殖、转化和癌变.AP-1属多基因家族,其活性受多种不同水平的调控.AP-1的活化促使下游靶基因如MMPs、整合素、CD44和VEGF等表达,在肿瘤恶性演进过程中参与了细胞基质降解、粘附功能异常、转移瘤新生血管生成、肿瘤细胞运动能力的增强等各个环节.AP-1信号转导通路的活化与肿瘤的发生、发展密切相关.     

Notch信号通路与消化道肿瘤

一直以来,肿瘤严重危害着人类的健康,有关肿瘤发病机制、治疗靶标的研究也成为科学研究的重点和热点之一.自1919年Notch基因在对果蝇的研究中被发现以来,越来越多的研究表明,Notch信号通路的异常激活或构成性活化与多种组织的肿瘤形成有关.     

多肿瘤抑制基因与肿瘤

多肿瘤抑制基因ｐ１６，ｐ１５是新近发现的一组抑癌基因，均位于人类染色体ｑｐ２１，在细胞周期的调控中起重要作用。它们在人体肿瘤和细胞系中有非常高的失活率，主要失活方式有基因纯合缺失，点突变，原位甲基化等     

Target genes of the WNT/beta-catenin pathway in Wilms tumors

The WNT/beta-catenin pathway is involved in numerous human cancers. Mutations of the CTNNB1 (beta-catenin) gene have also been detected in a subset of pediatric Wilms tumors, but the target genes of the deregulated WNT/beta-catenin pathway in these tumors have yet to be identified. To compare gene expression profiles of Wilms tumors with and without mutations of CTNNB1, we used 11.5-k cDNA microarrays. Most of the tumors (86%) had received preoperative chemotherapy as mandated by the European SIOP protocol. The comparison between Wilms tumors with and without CTNNB1 mutations revealed several target genes specifically deregulated in CTNNB1-mutated Wilms tumors. Among these, PITX2, APCDD1, and two members of the endothelin axis (EDN3 and EDNRA) are directly activated downstream targets of the WNT/beta-catenin pathway that may enhance proliferation of these tumor cells. In addition, several upstream inhibitors of WNT/beta-catenin signaling like WIF1 and PRDC were also strongly up-regulated in the CTNNB1-mutated Wilms tumors. This overexpression may be a negative feedback mechanism in tumors with uncontrolled WNT signaling. Moreover, we identified deregulated genes in both the retinoic acid and the RAS pathways, such as ATX/ENPP2 and RIS1, suggesting an association between these two pathways with that of WNT. In addition, the strong representation of muscle-related genes in the expression profile of CTNNB1-mutated Wilms tumors corresponded to histologically detectable areas of myomatous cells in these tumors that displayed intense and preferential nuclear beta-catenin antibody staining. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.     

Angioimmunoblastic T-cell lymphoma with dual genotype of TCR and IgH genes

A 70-year-old man complained of fever and sore throat accompanied by hoarseness of voice. On physical examination, there was no systemic abnormality but a mild lymphadenopathy of cervical lymph nodes. With laryngoscopy, there was a marked outgrowth of the bilateral palatine tonsils proximal to the vocal cord. The histology of the resected tumor was compatible with angioimmunoblastic T cell lymphoma (AITL), revealing the effacement of normal tonsillar architecture and small to medium-sized neoplastic cell proliferation around marked vascular proliferation and atrophic lymphoid follicles. Tumor cells were positive for conventional T-cell antigens as well as for the follicular helper T-cell marker, PD-1, and CXCL13. Large hodgkinoid cells, but no tumor cells, were positive for latent membrane protein-1 and Epstein-Barr virus-encoded small RNA (EBER)-1 (in situ hybridization). Non-neoplastic, double positive cells for EBER-1 and CD20 were also scattered. Southern blot analysis revealed dual TCR-Cβ1 and IGH-JH gene rearrangements. Although the swelling of bilateral inguinal and perigastric lymph nodes developed later, the radical resection of tumor and chemotherapy appeared to be effective for the treatment of AITL with clinical stage IIIa. We here report a rare case of AITL involving palatine tonsil as primary site and give a review of the literature.