Dermatology and Cutaneous Biology Research Center, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA.
J Clin Oncol. 2011 Sep 1;29(25):3474-82. doi: 10.1200/JCO.2010.32.6223. Epub 2011 Jun 13.
Members of the micropthalmia (MiT) family of transcription factors (MITF, TFE3, TFEB, and TFEC) are physiologic regulators of cell growth, differentiation, and survival in several tissue types. Because their dysregulation can lead to melanoma, renal cell carcinoma, and some sarcomas, understanding why these genes are co-opted in carcinogenesis may be of general utility. Here we describe the structure of the MiT family of proteins, the ways in which they are aberrantly activated, and the molecular mechanisms by which they promote oncogenesis. We discuss how meaningful understanding of these mechanisms can be used to elucidate the oncogenic process. Because the expression of these proteins is essential for initiating and maintaining the oncogenic state in some cancer types, we propose ways that they can be exploited to prevent, diagnose, and rationally treat these malignancies.
微眼畸形（MiT）家族的转录因子（MITF、TFE3、TFEB 和 TFEC）成员是几种组织类型中细胞生长、分化和存活的生理调节剂。由于它们的失调可导致黑色素瘤、肾细胞癌和一些肉瘤，因此了解这些基因为何在致癌作用中被共同选择可能具有普遍意义。在这里，我们描述了 MiT 家族蛋白的结构、它们异常激活的方式以及它们促进致癌作用的分子机制。我们讨论了如何利用这些机制的深入理解来阐明致癌过程。由于这些蛋白的表达对于某些癌症类型中起始和维持致癌状态是必需的，我们提出了利用它们来预防、诊断和合理治疗这些恶性肿瘤的方法。
