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• W1976713416 startingPage "615" @default.
• W1976713416 abstract "The p53 tumor suppressor gene is frequently mutated in multiple human cancers, leading to loss of wild-type p53 (wt-p53)-dependent functions and tumorigenesis. p53 gene therapy is used to induce apoptosis in human cancer cells and tumors. Activation of nuclear factor kappa B (NF-kappaB) causes resistance to both chemotherapy and apoptosis in tumor cells. We show that expression of wt-p53 from a recombinant adenovirus-p53 followed by treatment with 2-methoxyestradiol (2-ME), an endogenous, nontoxic, estrogenic metabolite, resulted in differential NF-kappaB activation and inhibitor kappaB alpha (IkappaB-alpha) degradation in three different human lung cancer cell lines with different p53 phenotypes. The H322J cells, with mutant (Arg248Gln) p53, showed NF-kappaB activation and IkappaB-alpha degradation after adeno-p53 expression + 2-ME treatment; however, these conditions separately did not activate NF-kappaB, rather caused accumulation of IkappaB-alpha. In contrast, either adeno-p53 expression or 2-ME treatment induced NF-kappaB activation in the p53-deleted H1299 cells, but H460 cells, containing wt-p53, did not show NF-kappaB activation under any of these conditions. This shows p53-dependent differential signaling to NF-kappaB by 2-ME. Since NF-kappaB activation inhibits apoptosis and causes resistance to chemotherapy, our study suggests the need to distinguish p53 phenotypes of tumors for p53 gene and 2-ME therapy." @default.
• W1976713416 created "2016-06-24" @default.
• W1976713416 creator A5030312949 @default.
• W1976713416 creator A5074849575 @default.
• W1976713416 date "2009-12-01" @default.
• W1976713416 modified "2023-09-25" @default.
• W1976713416 title "<i>p53</i>Gene Expression and 2-Methoxyestradiol Treatment Differentially Induce Nuclear Factor Kappa B Activation in Human Lung Cancer Cells with Different p53 Phenotypes" @default.
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• W1976713416 doi "https://doi.org/10.1089/dna.2008.0839" @default.
• W1976713416 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19715480" @default.
• W1976713416 hasPublicationYear "2009" @default.
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