https://scholars.lib.ntu.edu.tw/handle/123456789/596720
標題: | Aristolochic acid I interferes with the expression of BLCAP tumor suppressor gene in human cells | 作者: | Huang Y.-T. Wu T.-S. Lu C.-C. Yu F.-Y. Liu, Biing-Hui |
關鍵字: | Aristolochic acid; Bladder cancer associated protein; BLCAP; Carcinogenesis; HEK293 | 公開日期: | 2018 | 出版社: | Elsevier Ireland Ltd | 卷: | 291 | 起(迄)頁: | 129-137 | 來源出版物: | Toxicology Letters | 摘要: | Aristolochic acid I (AAI) is a phytocompound that is linked to the progressive renal disease and development of human urothelial carcinoma. The bladder cancer-associated protein (BLCAP) gene exhibits a tumor suppressor function in various tumors, including bladder carcinoma. This study evaluated the effect of AAI on BLCAP expression and its associated mechanism in human cells. Administering AAI to human embryonic kidney cells (HEK293), human proximal tubule epithelial cells (HK-2) and urinary bladder cancer cells (HT-1376) significantly reduced the expression of BLCAP mRNA and protein. AAI also effectively suppressed the luciferase activities driven by BLCAP promoters of various lengths in HEK293 cells. AAI significantly reduced both activator protein 1 (AP-1) and nuclear factor-κB (NF-κB) activities in reporter assays, but further point mutations revealed that Ap-1 and NF-κB binding sites on the BLCAP promoter were not AAI-responsive elements. Application of the DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC), reversed the decline of BLCAP expression that had been induced by AAI. However, AAI exposure did not alter hypermethylation of the BLCAP promoter, determined by methyl-specific polymerase chain reaction (PCR) and bisulfate sequencing. Knocking down BLCAP in HEK293 cell line enhanced the potential for cellular migration, invasion, and proliferation, along with the induction of a capacity for anchorage-independent growth. In conclusion, AAI down-regulated the expression of BLCAP gene and the deficiency in BLCAP expression contributed to the malignant transformation of human cells, implying that BLCAP may have a role in mediating AAI-associated carcinogenesis. ? 2018 Elsevier B.V. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046014677&doi=10.1016%2fj.toxlet.2018.03.032&partnerID=40&md5=8ee0373a2c1b1433f34f75c17904dd13 https://scholars.lib.ntu.edu.tw/handle/123456789/596720 |
ISSN: | 0378-4274 | DOI: | 10.1016/j.toxlet.2018.03.032 | SDG/關鍵字: | aristolochic acid; aristolochic acid i; decitabine; immunoglobulin enhancer binding protein; luciferase; messenger RNA; transcription factor AP 1; unclassified drug; 5-aza-2'-deoxycytidine-5'-monophosphate; aristolochic acid; aristolochic acid I; azacitidine; BLCAP protein, human; enzyme inhibitor; immunoglobulin enhancer binding protein; messenger RNA; transcription factor AP 1; tumor protein; anchorage independent growth; Article; binding site; bladder cancer; bladder cancer associated protein gene; cell invasion; cell migration; cell proliferation; controlled study; drug mechanism; enzyme activity; epigenetics; gene expression; genetic regulation; HEK293 cell line; HT-1376 cell line; human; human cell; kidney cancer; kidney proximal tubule; kidney tubule cell; kidney tubule epithelium; luciferase assay; point mutation; polymerase chain reaction; priority journal; promoter region; tumor suppressor gene; analogs and derivatives; antagonists and inhibitors; biosynthesis; cell motion; cell survival; drug effect; gene expression regulation; gene knockdown; genetics; Aristolochic Acids; Azacitidine; Binding Sites; Cell Movement; Cell Survival; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; HEK293 Cells; Humans; Neoplasm Proteins; NF-kappa B; Point Mutation; Promoter Regions, Genetic; RNA, Messenger; Transcription Factor AP-1 |
顯示於: | 毒理學研究所 |
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