文章：

ABCB1基因在癌症中的遗传学研究

Genetics ofABCB1in Cancer

原文发布日期：24 August 2023

DOI: 10.3390/cancers15174236

类型: Article

开放获取: 是

英文摘要：

ABCB1, also known asMDR1, is a gene that encodes P-glycoprotein (P-gp), a membrane-associated ATP-dependent transporter. P-gp is widely expressed in many healthy tissues—in the gastrointestinal tract, liver, kidney, and at the blood–brain barrier. P-gp works to pump xenobiotics such as toxins and drugs out of cells. P-gp is also commonly upregulated across multiple cancer types such as ovarian, breast, and lung. Overexpression ofABCB1has been linked to the development of chemotherapy resistance across these cancers. In vitro work across a wide range of drug-sensitive and -resistant cancer cell lines has shown that upon treatment with chemotherapeutic agents such as doxorubicin, cisplatin, and paclitaxel,ABCB1is upregulated. This upregulation is caused in part by a variety of genetic and epigenetic mechanisms. This includes single-nucleotide variants that lead to enhanced P-gp ATPase activity without increasingABCB1RNA and protein levels. In this review, we summarize current knowledge of genetic and epigenetic mechanisms leading toABCB1upregulation and P-gp-enhanced ATPase activity in the setting of chemotherapy resistance across a variety of cancers.

摘要翻译： 

ABCB1，亦称多药耐药基因1（MDR1），其编码产物为P-糖蛋白（P-gp）。该蛋白是一种膜结合型ATP依赖性转运蛋白，广泛表达于胃肠道、肝脏、肾脏及血脑屏障等多种正常组织中，其功能主要在于将毒素、药物等外源性物质泵出细胞。值得注意的是，P-gp在卵巢癌、乳腺癌及肺癌等多种恶性肿瘤中常呈现高表达状态。研究表明，ABCB1的过度表达与上述癌症化疗耐药性的产生密切相关。通过对大量药物敏感及耐药癌细胞系的体外实验发现，经阿霉素、顺铂、紫杉醇等化疗药物处理后，ABCB1表达水平显著上调。这种上调现象部分归因于多种遗传学与表观遗传学机制，其中包括某些单核苷酸变异——这些变异在不增加ABCB1 RNA及蛋白表达水平的情况下，仍能增强P-gp的ATP酶活性。本文综述了当前关于各类癌症化疗耐药背景下，导致ABCB1上调及P-gp ATP酶活性增强的遗传与表观遗传机制的研究进展。

原文链接：

Genetics ofABCB1in Cancer