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Unraveling the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) expression in colon carcinogenesis
npj Precision Oncology ( IF 7.9 ) Pub Date : 2019-10-07 , DOI: 10.1038/s41698-019-0098-x
Jeffrey M. Peters , Vonn Walter , Andrew D. Patterson , Frank J. Gonzalez

The peroxisome proliferator-activated-β/δ (PPARβ/δ) was identified in 1994, but not until 1999 was PPARβ/δ suggested to be involved in carcinogenesis. Initially, it was hypothesized that expression of PPARβ/δ was increased during colon cancer progression, which led to increased transcription of yet-to-be confirmed target genes that promote cell proliferation and tumorigenesis. It was also hypothesized at this time that lipid-metabolizing enzymes generated lipid metabolites that served as ligands for PPARβ/δ. These hypothetical mechanisms were attractive because they potentially explained how non-steroidal anti-inflammatory drugs inhibited tumorigenesis by potentially limiting the concentration of endogenous PPARβ/δ ligands that could activate this receptor that was increased in cancer cells. However, during the last 20 years, considerable research was undertaken describing expression of PPARβ/δ in normal and cancer cells that has led to a significant impact on the mechanisms by which PPARβ/δ functions in carcinogenesis. Whereas results from earlier studies led to much uncertainty about the role of PPARβ/δ in cancer, more recent analyses of large databases have revealed a more consistent understanding. The focus of this review is on the fundamental level of PPARβ/δ expression in normal tissues and cancerous tissue as described by studies during the past two decades and what has been delineated during this timeframe about how PPARβ/δ expression influences carcinogenesis, with an emphasis on colon cancer.



中文翻译:

揭示过氧化物酶体增殖物激活的受体-β/δ(PPARβ/δ)表达在结肠癌发生中的作用

过氧化物酶体增殖物激活的β/δ(PPARβ/δ)于1994年发现,但直到1999年才提示PPARβ/δ参与致癌作用。最初,有人假设在结肠癌进展期间PPARβ/δ的表达增加,这导致尚未证实的促进细胞增殖和肿瘤发生的靶基因的转录增加。此时还假设脂质代谢酶产生脂质代谢产物,该代谢产物充当PPARβ/δ的配体。这些假设机制之所以具有吸引力,是因为它们潜在地解释了非甾体类抗炎药如何通过潜在地限制内源性PPARβ/δ配体的浓度来抑制肿瘤发生,该内源性PPARβ/δ配体可以激活这种在癌细胞中增加的受体。但是,在过去的20年中,进行了大量的研究来描述PPARβ/δ在正常细胞和癌细胞中的表达,这已对PPARβ/δ在癌变中起作用的机制产生了重大影响。早期研究的结果导致有关PPARβ/δ在癌症中作用的不确定性,而最近对大型数据库的分析则显示出更加一致的理解。这篇综述的重点是正常组织和癌组织中PPARβ/δ表达的基本水平,如过去二十年来的研究所描述的,以及在此时间范围内关于PPARβ/δ表达如何影响癌变的研究内容,重点是对结肠癌。

更新日期:2019-10-07
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