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Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay
Cancer Cell International ( IF 5.8 ) Pub Date : 2020-03-04 , DOI: 10.1186/s12935-020-1153-y
Aarifa Nazmeen 1 , Guangping Chen 2 , Tamal Kanti Ghosh 3 , Smarajit Maiti 1, 4
Affiliation  

Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Sulfoconjugated estrogen fails to bind estrogen-receptor (ER). High estrogen is a known carcinogen in postmenopausal women. Reports reveal a potential redox-regulation of hSULT1E1/E2-signalling. Further, oxidatively-regulated nuclear-receptor-factor 2 (Nrf2) and NFκβ in relation to hSULT1E1/E2 could be therapeutic-target via cellular redox-modification. Here, oxidative stress-regulated SULT1E1-expression was analyzed in human breast carcinoma-tissues and in rat xenografted with human breast-tumor. Tumor and its surrounding tissues were obtained from the district-hospital. Intracellular redox-environment of tumors was screened with some in vitro studies. RT-PCR and western blotting was done for SULT1E1 expression. Immunohistochemistry was performed to analyze SULT1E1/Nrf2/NFκβ localization. Tissue-histoarchitecture/DNA-stability (comet assay) studies were done. Oxidative-stress induces SULT1E1 via Nrf2/NFκβ cooperatively in tumor-pathogenesis to maintain the required proliferative-state under enriched E2-environment. Higher malondialdehyde/non-protein-soluble-thiol with increased superoxide-dismutase/glutathione-peroxidase/catalase activities was noticed. SULT1E1 expression and E2-level were increased in tumor-tissue compared to their corresponding surrounding-tissues. It may be concluded that tumors maintain a sustainable oxidative-stress through impaired antioxidants as compared to the surrounding. Liver-tissues from xenografted rat manifested similar E2/antioxidant dysregulations favoring pre-tumorogenic environment.

中文翻译:

乳腺癌发病机制与肿瘤内雌激素磺基转移酶 (hSULT1E1) 表达有关,该酶受细胞氧化还原依赖性 Nrf-2/NFκβ 相互作用的调节

雌激素磺基转移酶催化硫酰基与雌二醇/雌酮的结合,并通过雌激素受体或非受体介导的途径调节 E2 的可用性/活性。磺基结合雌激素无法结合雌激素受体 (ER)。高雌激素是绝经后妇女已知的致癌物质。报告揭示了 hSULT1E1/E2 信号传导的潜在氧化还原调节。此外,与 hSULT1E1/E2 相关的氧化调节核受体因子 2 (Nrf2) 和 NFκβ 可以通过细胞氧化还原修饰成为治疗靶点。在这里,我们分析了人乳腺癌组织和异种移植人乳腺肿瘤的大鼠中氧化应激调节的 SULT1E1 表达。肿瘤及其周围组织获自地区医院。通过一些体外研究筛选了肿瘤的细胞内氧化还原环境。对 SULT1E1 表达进行 RT-PCR 和蛋白质印迹分析。进行免疫组织化学分析 SULT1E1/Nrf2/NFκβ 定位。进行了组织组织结构/DNA 稳定性(彗星测定)研究。氧化应激通过 Nrf2/NFκβ 在肿瘤发病机制中协同诱导 SULT1E1,以在丰富的 E2 环境下维持所需的增殖状态。注意到较高的丙二醛/非蛋白质可溶性硫醇以及超氧化物歧化酶/谷胱甘肽过氧化物酶/过氧化氢酶活性增加。与相应的周围组织相比,肿瘤组织中的 SULT1E1 表达和 E2 水平增加。可以得出结论,与周围环境相比,肿瘤通过受损的抗氧化剂维持可持续的氧化应激。异种移植大鼠的肝组织表现出类似的 E2/抗氧化失调,有利于肿瘤发生前的环境。
更新日期:2020-03-06
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