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[甲状腺癌中的细胞内信号传导机制]

[Intracellular signaling mechanisms in thyroid cancer].

作者信息

Mondragón-Terán Paul, López-Hernández Luz Berenice, Gutiérrez-Salinas José, Suárez-Cuenca Juan Antonio, Luna-Ceballos Rosa Isela, Erazo Valle-Solís Aura

机构信息

Laboratorio de Medicina Regenerativa e Ingeniería de Tejidos, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México; Subdirección de Investigación y Enseñanza, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México.

División de Investigación Biomédica, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México; Subdirección de Investigación y Enseñanza, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México.

出版信息

Cir Cir. 2016 Sep-Oct;84(5):434-43. doi: 10.1016/j.circir.2016.05.017. Epub 2016 Aug 8.

DOI:10.1016/j.circir.2016.05.017
PMID:
27423883
Abstract

BACKGROUND

Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis.

OBJECTIVE

To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer.

CONCLUSIONS

Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway.

摘要

背景

甲状腺癌是内分泌系统最常见的恶性肿瘤,乳头状甲状腺癌占所有确诊病例的80 - 90%。在乳头状甲状腺癌的发展过程中,BRAF和RAS基因主要受到影响,导致一种称为“丝裂原活化蛋白激酶”(MAPK)的细胞内信号蛋白系统发生改变,该系统由从细胞膜到细胞核的细胞内信号蛋白(受体/ Ras / Raf / MEK / ERK)“模块”组成。在甲状腺癌中,这些信号蛋白调节多种细胞过程,如分化、生长、发育和凋亡。MAPK在甲状腺癌的发病机制中起重要作用,因为它们被用作诊断、预后的分子生物标志物以及可能的治疗分子靶点。BRAF基因的突变与传统化疗治疗反应不佳相关,并且是预后不良的指标。

目的

综述甲状腺癌中BRAF和RAS基因细胞内信号传导的分子机制。

结论

针对这类癌症的分子治疗研究正在进行中,因为已经开发出了新的分子来抑制信号通路(RET / PTC)/ Ras / Raf / MEK / ERK的任何成分;特别强调(RET / PTC)/ Ras / Raf部分,它是ERK途径的主要效应器。

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[Intracellular signaling mechanisms in thyroid cancer].[甲状腺癌中的细胞内信号传导机制]
Cir Cir. 2016 Sep-Oct;84(5):434-43. doi: 10.1016/j.circir.2016.05.017. Epub 2016 Aug 8.
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Genetic alterations in the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathways in the follicular variant of papillary thyroid carcinoma.滤泡型甲状腺乳头状癌中 RAS/RAF/丝裂原活化蛋白激酶和磷脂酰肌醇 3-激酶/蛋白激酶 B 信号通路的遗传改变。
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[The mitogen-activated protein kinase (MAPK) signaling pathway in papillary thyroid cancer. From the molecular bases to clinical practice].[甲状腺乳头状癌中的丝裂原活化蛋白激酶(MAPK)信号通路。从分子基础到临床实践]
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J Clin Endocrinol Metab. 2012 Jun;97(6):E898-906. doi: 10.1210/jc.2011-3269. Epub 2012 Mar 22.
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Front Biosci (Landmark Ed). 2011 Jan 1;16(2):422-39. doi: 10.2741/3696.
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Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo.Raf激酶活性抑制剂在体外和体内均可阻断具有RET/PTC或BRAF突变的甲状腺癌细胞的生长。
Clin Cancer Res. 2006 Mar 15;12(6):1785-93. doi: 10.1158/1078-0432.CCR-05-1729.
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E26 transformation (ETS)‑specific related transcription factor‑3 (ELF3) orchestrates a positive feedback loop that constitutively activates the MAPK/Erk pathway to drive thyroid cancer.E26 转化(ETS)特异性相关转录因子 3(ELF3)协调一个正反馈回路,该回路持续激活 MAPK/Erk 通路以驱动甲状腺癌。
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BRAF mediates RET/PTC-induced mitogen-activated protein kinase activation in thyroid cells: functional support for requirement of the RET/PTC-RAS-BRAF pathway in papillary thyroid carcinogenesis.BRAF介导甲状腺细胞中RET/PTC诱导的丝裂原活化蛋白激酶激活:对甲状腺乳头状癌发生中RET/PTC-RAS-BRAF途径需求的功能支持。
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