Pappou Emmanouil P, Ahuja Nita
Department of Surgery The Johns Hopkins University Baltimore, MD.
Gastrointest Cancer Res. 2010 Nov(Suppl 1):S2-S15.
Oncogene research over the last century has been one of the major advances in understanding the molecular biology of malignant disease. Oncogenes are a structurally and functionally heterogeneous group of genes, whose protein products act pleiotropically and affect multiple complex regulatory cascades within the cell. They regulate cell proliferation, growth, and differentiation, as well as control of the cell cycle and apoptosis. The products of oncogenes include growth factors, growth factor receptors, signal transducers, transcription factors, and apoptosis regulators, as well as chromatin remodelers. Several distinct mechanisms have been described for the conversion of proto-oncogenes to active oncogenes. Quantitative forms of oncogene activation include multiplication (gene amplification) or translocation to an active chromatin domain that brings a growth-regulatory gene under the control of a different promoter, causing inappropriate expression of the gene. Qualitative forms include either point mutations or the production of a novel product from a chimeric gene. Further understanding of the molecular mechanisms by which oncogenes regulate normal development and tumorigenesis may lead to novel concepts in the diagnosis and treatment of cancer in humans. In this review, we focus on the role of selected oncogenes in gastrointestinal cancer.
上个世纪的癌基因研究是理解恶性疾病分子生物学方面的重大进展之一。癌基因是一组在结构和功能上具有异质性的基因，其蛋白质产物具有多效性，可影响细胞内多个复杂的调控级联反应。它们调节细胞增殖、生长和分化，以及细胞周期和细胞凋亡的控制。癌基因的产物包括生长因子、生长因子受体、信号转导子、转录因子和凋亡调节因子，以及染色质重塑因子。已经描述了几种将原癌基因转化为活性癌基因的不同机制。癌基因激活的定量形式包括倍增（基因扩增）或易位至活性染色质结构域，使生长调节基因受不同启动子控制，导致该基因表达异常。定性形式包括点突变或嵌合基因产生新产物。对癌基因调节正常发育和肿瘤发生的分子机制的进一步了解可能会带来人类癌症诊断和治疗的新概念。在本综述中，我们重点关注特定癌基因在胃肠道癌中的作用。
