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[恶性黑色素瘤与矛盾蛋白小眼转录因子的作用]

[Malignant melanoma and the role of the paradoxal protein Microphthalmia transcription factor].

作者信息

Denat Laurence, Larue Lionel

机构信息

Developmental Genetics of Melanocytes, UMR146 CNRS, Institut Curie, Bât. 110, 91405, Orsay Cedex.

出版信息

Bull Cancer. 2007 Jan;94(1):81-92.

Abstract

Mitf protein is a transcription factor involved all along the life of pigmented cells. This protein is located in the center of multiple signaling pathways which control differentiation, morphology, proliferation and survival of the various cells of the melanocyte lineage: melanoblasts, melanocytes and melanoma. Mitf plays a major role in melanoblasts differentiation, by inducing the key enzyme of melanogenesis, tyrosinase, and its secondary enzymes, Tyrp1 and Dct. Mitf regulates morphology and migration of melanocytes, particularly by regulating cytoskeleton organization and cell-cell adhesion. Mitf plays a double role of inducer/repressor of cellular proliferation. This protein inhibits cell cycle progression and prevents non-proper cell division. In few cases, Mitf can also induce cell cycle. A minimal quantity/activity of Mitf is necessary for melanoblast survival. Essential protein of the melanocyte lineage, Mitf was proposed as diagnostic/pronostic marker for cutaneous melanoma. However, could we then consider MITF as the unique marker of such a cancer?

摘要

小眼畸形相关转录因子(Mitf)蛋白是一种在色素细胞整个生命周期中都发挥作用的转录因子。该蛋白位于多个信号通路的中心,这些信号通路控制着黑素细胞谱系中各种细胞(黑素母细胞、黑素细胞和黑色素瘤细胞)的分化、形态、增殖和存活。Mitf在黑素母细胞分化中起主要作用,它能诱导黑素生成的关键酶酪氨酸酶及其辅助酶酪氨酸酶相关蛋白1(Tyrp1)和二羟基吲哚羧酸(Dct)。Mitf调节黑素细胞的形态和迁移,特别是通过调节细胞骨架组织和细胞间黏附来实现。Mitf在细胞增殖中扮演诱导剂/抑制剂的双重角色。这种蛋白会抑制细胞周期进程并防止细胞异常分裂。在少数情况下,Mitf也能诱导细胞周期。黑素母细胞存活需要最低量的Mitf蛋白或其活性。作为黑素细胞谱系的关键蛋白,Mitf被提议作为皮肤黑色素瘤的诊断/预后标志物。然而,我们能因此将MITF视为这种癌症的唯一标志物吗?

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