Lang Deborah, Powell Sara K, Plummer Rebecca S, Young Kacey P, Ruggeri Bruce A
University of Chicago, Department of Medicine, Section of Dermatology, 5841 S. Maryland Avenue, Chicago, IL 60637, United States.
Biochem Pharmacol. 2007 Jan 1;73(1):1-14. doi: 10.1016/j.bcp.2006.06.024. Epub 2006 Aug 14.
PAX proteins function as transcription factors and play an essential role in organogenesis during embryonic development in regulating cell proliferation and self-renewal, resistance to apoptosis, migration of embryonic precursor cells, and the coordination of specific differentiation programs. Recent studies have also discovered a role for PAX proteins in specific stem cell or progenitor cell populations, including melanocytes, muscle, and B-cells. The normal functions of the PAX proteins, including apoptosis resistance and repression of terminal differentiation, may be subverted during the progression of a number of specific malignancies. This is supported by the fact that expression of PAX proteins is dysregulated in several different types of tumors, although the precise roles for PAX proteins in cancer are not clearly understood. An emerging hypothesis is that PAX proteins play an essential role in maintaining tissue specific stem cells by inhibiting terminal differentiation and apoptosis and that these functional characteristics may facilitate the development and progression of specific cancers. In this review, we provide a general background to the PAX protein family and focus on specific cells and tissues and the role PAX proteins play within these tissues in terms of development, mature tissue maintenance, and expression in tumors. Understanding the normal developmental pathways regulated by PAX proteins may shed light on potentially parallel pathways shared in tumors, and ultimately result in defining new molecular targets and signaling pathways for the development of novel anti-cancer therapies.
PAX蛋白作为转录因子发挥作用，在胚胎发育过程中的器官形成中，对调节细胞增殖和自我更新、抗凋亡能力、胚胎前体细胞迁移以及特定分化程序的协调起着至关重要的作用。最近的研究还发现PAX蛋白在特定的干细胞或祖细胞群体中发挥作用，包括黑素细胞、肌肉和B细胞。在许多特定恶性肿瘤的进展过程中，PAX蛋白的正常功能，包括抗凋亡和抑制终末分化，可能会被颠覆。这一点得到了以下事实的支持：PAX蛋白的表达在几种不同类型的肿瘤中失调，尽管PAX蛋白在癌症中的精确作用尚不清楚。一个新出现的假说是，PAX蛋白通过抑制终末分化和凋亡在维持组织特异性干细胞方面发挥重要作用，并且这些功能特性可能促进特定癌症的发生和发展。在这篇综述中，我们提供了PAX蛋白家族的一般背景，并聚焦于特定细胞和组织，以及PAX蛋白在这些组织的发育、成熟组织维持和肿瘤表达方面所起的作用。了解由PAX蛋白调节的正常发育途径可能会揭示肿瘤中潜在的平行途径，并最终有助于确定新的分子靶点和信号通路，以开发新的抗癌疗法。
