Rayburn Elizabeth, Zhang Ruiwen, He Jie, Wang Hui
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA.
Curr Cancer Drug Targets. 2005 Feb;5(1):27-41. doi: 10.2174/1568009053332636.
The human homologue of the mouse double minute 2 (MDM2) oncogene is overexpressed in more than forty different types of malignancies, including solid tumors, sarcomas and leukemias. Because of its prevalent expression and its interactions with p53 and other signaling molecules, MDM2 plays a central role in cancer development and progression. The expression of this oncoprotein is being studied by researchers world-wide, and the amount of data published about it is increasing exponentially. Although there are some conflicting data about the effects of MDM2 expression in individual cancers, the overall evidence is convincing, indicating that increased MDM2 expression is related to a worse clinical prognosis. There is an increased likelihood of distant metastases, as well as a decreased response to therapeutic intervention in MDM2-positive cancers. MDM2 may also serve as a diagnostic marker, not only for cancer stage, but to differentiate between similar cancers. MDM2 may also be associated with drug resistance in cancer chemotherapy. These findings make studying the oncoprotein necessary to aid in our understanding of cancer development, to identify novel cancer drug targets, and to increase the efficacy of cancer therapy.
小鼠双微体2（MDM2）癌基因的人类同源物在四十多种不同类型的恶性肿瘤中过表达，包括实体瘤、肉瘤和白血病。由于其广泛表达以及与p53和其他信号分子的相互作用，MDM2在癌症发生和发展中起着核心作用。世界各地的研究人员都在研究这种癌蛋白的表达情况，关于它的已发表数据量呈指数级增长。尽管关于MDM2表达在个别癌症中的影响存在一些相互矛盾的数据，但总体证据令人信服，表明MDM2表达增加与较差的临床预后相关。在MDM2阳性癌症中，远处转移的可能性增加，对治疗干预的反应降低。MDM2还可作为一种诊断标志物，不仅用于癌症分期，还用于区分相似的癌症。MDM2也可能与癌症化疗中的耐药性有关。这些发现使得研究这种癌蛋白对于帮助我们理解癌症发展、识别新的癌症药物靶点以及提高癌症治疗效果变得必要。
