DNA and cell biology
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DNA and cell biology · Dec 2009
p53 gene expression and 2-methoxyestradiol treatment differentially induce nuclear factor kappa B activation in human lung cancer cells with different p53 phenotypes.
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. ⋯ 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.