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http://purl.uniprot.org/citations/17560011http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17560011http://www.w3.org/2000/01/rdf-schema#comment"

Objective

AML1-ETO fusion protein is a product of chromosome translocation t(8;21) frequently occurred in acute myeloid leukemia (AML), but its sole expression appears to fail to cause overt leukemia in vivo. In this study, we investigated whether AML1-ETO expression impinged on action of chemical carcinogens-DNA adduct formation.

Materials and methods

AML1-ETO fusion protein was conditionally induced in engineered U937-A/E 9/14/18 cells. The formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts and the expression of PAH-metabolizing enzymes cytochrome P450 (CYP) 1A1 and arylhydrocarbon receptor (AhR) were detected by Western blot and/or quantitative RT-PCR. Luciferase reporter system was used to detect the regulation of AML1-ETO on CYP1A1 transcription.

Results

Our results showed that AML1-ETO induction significantly increased the formation of carcinogen benzopyrene-DNA adducts in leukemic cells. In line with the effect, we also found that AML1-ETO induction upregulated CYP1A1 expression, which was dependent on AML1-binding motif in the promotor of CYP1A1 gene. Additionally, AML1-ETO protein also increased AhR expression, a ligand-activated transcription factor that mediates PAHs-induced CYP1A1 gene expression.

Conclusion

These data, combined with its inhibitory effect on DNA repair as reported previously, propose that the presence of AML1-ETO increases the susceptibility of cells to chemical carcinogens, which favors the development of additional genetic alterations."xsd:string
http://purl.uniprot.org/citations/17560011http://purl.org/dc/terms/identifier"doi:10.1016/j.exphem.2007.04.018"xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/author"Chen G.Q."xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/author"Lu Y."xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/author"Li D."xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/author"Xu M."xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/name"Exp Hematol"xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/pages"1249-1255"xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/title"Leukemogenic AML1-ETO fusion protein increases carcinogen-DNA adduct formation with upregulated expression of cytochrome P450-1A1 gene."xsd:string
http://purl.uniprot.org/citations/17560011http://purl.uniprot.org/core/volume"35"xsd:string
http://purl.uniprot.org/citations/17560011http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17560011
http://purl.uniprot.org/citations/17560011http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17560011
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http://purl.uniprot.org/uniprot/#_Q71VC2-mappedCitation-17560011http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17560011
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