The nuclear factor erythroid 2-related factor 2/p53 axis in breast cancer.

Lei Xia, Wenbiao Ma, Ahmad Afrashteh, Mir Amirhossein Sajadi, Hadi Fakheri, Mohammad Valilo
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Abstract

One of the most important factors involved in the response to oxidative stress (OS) is the nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the expression of components such as antioxidative stress proteins and enzymes. Under normal conditions, Kelch-like ECH-associated protein 1 (Keap1) keeps Nrf2 in the cytoplasm, thus preventing its translocation to the nucleus and inhibiting its role. It has been established that Nrf2 has a dual function; on the one hand, it promotes angiogenesis and cancer cell metastasis while causing resistance to drugs and chemotherapy. On the other hand, Nrf2 increases expression and proliferation of glutathione to protect cells against OS. p53 is a tumour suppressor that activates the apoptosis pathway in aging and cancer cells in addition to stimulating the glutaminolysis and antioxidant pathways. Cancer cells use the antioxidant ability of p53 against OS. Therefore, in the present study, we discussed function of Nrf2 and p53 in breast cancer (BC) cells to elucidate their role in protection or destruction of cancer cells as well as their drug resistance or antioxidant properties.

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核因子红细胞2型相关因子2/p53轴在癌症中的表达。
参与氧化应激反应的最重要因素之一是核因子红系2相关因子2(Nrf2),它调节抗氧化应激蛋白和酶等成分的表达。在正常条件下,Kelch样ECH相关蛋白1(Keap1)将Nrf2保持在细胞质中,从而阻止其易位到细胞核并抑制其作用。已经证实Nrf2具有双重功能;一方面,它促进血管生成和癌症细胞转移,同时引起对药物和化疗的耐药性。另一方面,Nrf2增加谷胱甘肽的表达和增殖,以保护细胞免受OS的侵害。p53是一种肿瘤抑制因子,除了刺激谷氨酸解和抗氧化途径外,它还能激活衰老和癌症细胞的凋亡途径。癌症细胞利用p53对OS的抗氧化能力。因此,在本研究中,我们讨论了Nrf2和p53在癌症(BC)细胞中的功能,以阐明它们在保护或破坏癌症细胞中的作用以及它们的耐药性或抗氧化特性。
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