PML: An emerging tumor suppressor and a target with therapeutic potential.

Cancer therapy Pub Date : 2009-09-01
Erin L Reineke, Hung-Ying Kao
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Abstract

Though originally discovered as a tumor suppressor in Acute Promyelocytic Leukemia (APL), the importance of promyelocytic leukemia protein (PML) in cancers of other origins has not been widely studied. Recent studies have shown that multiple types of cancers show decreased expression of PML protein, though the mechanisms leading to this down-regulation are unknown. Decreased expression of PML can result in loss of cell cycle control and prevention of apoptosis and is likely a key event in the promotion of oncogenesis. Many of these effects are due to changes in the transcriptional profile of the cell as a result of decreased size and number of PML nuclear bodies. Several mouse studies confirm the contribution of PML to oncogenesis and cancer progression. It is important to not only further define a role for PML as a tumor suppressor, but also to begin to develop strategies to target PML therapeutically.

Abstract Image

Abstract Image

PML:一种新兴的肿瘤抑制因子和具有治疗潜力的靶点。
虽然早幼粒细胞白血病蛋白(PML)最初是作为一种肿瘤抑制因子在急性早幼粒细胞白血病(APL)中发现的,但其在其他起源癌症中的重要性尚未得到广泛研究。最近的研究表明,多种类型的癌症显示PML蛋白的表达下降,尽管导致这种下调的机制尚不清楚。PML的表达降低可导致细胞周期控制和细胞凋亡的丧失,可能是促进肿瘤发生的关键事件。许多这些影响是由于细胞转录谱的变化,因为PML核体的大小和数量减少。几项小鼠研究证实了PML对肿瘤发生和癌症进展的贡献。重要的是不仅要进一步确定PML作为肿瘤抑制因子的作用,而且要开始制定针对PML的治疗策略。
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