Seth Arun, Watson Dennis K
Molecular and Cellular Biology Research, Laboratory of Molecular Pathology, Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
Eur J Cancer. 2005 Nov;41(16):2462-78. doi: 10.1016/j.ejca.2005.08.013. Epub 2005 Oct 6.
Cancer can be defined as a genetic disease, resulting as a consequence of multiple events associated with initiation, promotion and metastatic growth. Cancer results from the loss of control of cellular homeostasis. Cell homeostasis is the result of the balance between proliferation and cell death, while cellular transformation can be viewed as a loss of relationship between these events. Oncogenes and tumour suppressor genes act as modulators of cell proliferation, while the balance of apoptotic and anti-apoptotic genes controls cell death. All cancer cells acquire similar sets of functional capacities: (1) independence from mitogenic/growth signals; (2) loss of sensitivity to "anti-growth" signals; (3) evade apoptosis; (4) Neo-angiogenic conversion; (5) release from senescence; and (6) invasiveness and metastasis. One of the goals of molecular biology is to elucidate the mechanisms that contribute to the development and progression of cancer. Such understanding of the molecular basis of cancer will provide new possibilities for: (1) earlier detection as well as better diagnosis and staging of disease with detection of minimal residual disease recurrences and evaluation of response to therapy; (2) prevention; and (3) novel treatment strategies. We feel that increased understanding of ETS-regulated biological pathways will directly impact these areas. ETS proteins are transcription factors that activate or repress the expression of genes that are involved in various biological processes, including cellular proliferation, differentiation, development, transformation and apoptosis. Identification of target genes that are regulated by a specific transcription factor is one of the most critical areas in understanding the molecular mechanisms that control transcription. Furthermore, identification of target gene promoters for normal and oncogenic transcription factors provides insight into the regulation of genes that are involved in control of normal cell growth, and differentiation, as well as provide information critical to understanding cancer development. This review will highlight the current understanding of ETS genes and their role in cancer.
癌症可被定义为一种遗传性疾病，它是由与起始、促进和转移生长相关的多个事件导致的。癌症源于细胞稳态控制的丧失。细胞稳态是增殖与细胞死亡之间平衡的结果，而细胞转化可被视为这些事件之间关系的丧失。癌基因和肿瘤抑制基因作为细胞增殖的调节因子，而凋亡基因和抗凋亡基因的平衡控制细胞死亡。所有癌细胞都获得了相似的一组功能能力：（1）不依赖有丝分裂/生长信号；（2）对“抗生长”信号失去敏感性；（3）逃避凋亡；（4）新血管生成转化；（5）从衰老中释放；以及（6）侵袭和转移。分子生物学的目标之一是阐明促成癌症发生和发展的机制。对癌症分子基础的这种理解将为以下方面提供新的可能性：（1）通过检测最小残留疾病复发和评估对治疗的反应，实现更早的检测以及更好的疾病诊断和分期；（2）预防；以及（3）新的治疗策略。我们认为，对ETS调节的生物学途径的深入理解将直接影响这些领域。ETS蛋白是转录因子，可激活或抑制参与各种生物学过程的基因的表达，这些过程包括细胞增殖、分化、发育、转化和凋亡。鉴定受特定转录因子调控的靶基因是理解控制转录的分子机制的最关键领域之一。此外，鉴定正常和致癌转录因子的靶基因启动子，有助于深入了解参与正常细胞生长和分化控制的基因的调控，同时也为理解癌症发展提供关键信息。本综述将重点介绍对ETS基因及其在癌症中的作用的当前认识。
