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• W2911142703 endingPage "9137" @default.
• W2911142703 startingPage "9125" @default.
• W2911142703 abstract "Abstract Fragile histidine trail (FHIT) is a tumor suppressor in response to DNA damage which has been deleted in various tumors. However, the signaling mechanisms and interactions of FHIT with regard to apoptotic proteins including p53 and p38 in the DNA damage‐induced apoptosis are not well described. In the present study, we used etoposide‐induced DNA damage in MCF‐7 as a model to address these crosstalks. The time course study showed that the expression of FHIT, p53, and p38MAPK started after 1 hour following etoposide treatment. FHIT overexpression led to increase p53 expression, p38 activation, and augmented apoptosis following etoposide‐induced DNA damage compared to wild‐type cells. However, FHIT knockdown blocked p53 expression, delayed p38 activation, and completely inhibited etoposide‐induced apoptosis. Inhibition of p38 activity prevented induction of p53, FHIT, and apoptosis in this model. Thus, activation of p38 upon etoposide treatment leads to increase in FHIT and p53 expression. In p53 knockdown MCF‐7, the FHIT induction was hampered but p38 activation was induced in lower doses of etoposide. In p53 knockdown cells, inhibition of p38 induced FHIT expression and apoptosis. Our data demonstrated that the exposure of MCF‐7 cells to etoposide increases apoptosis through a mechanism involving the activation of the p38‐FHIT‐p53 pathway. Moreover, our findings suggest signaling interaction for these pathways may represent a promising therapy for breast cancer." @default.
• W2911142703 created "2019-01-25" @default.
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• W2911142703 date "2019-01-04" @default.
• W2911142703 modified "2023-10-16" @default.
• W2911142703 title "Signaling Crosstalk of FHIT, p53, and p38 in etoposide‐induced apoptosis in MCF‐7 cells" @default.
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• W2911142703 doi "https://doi.org/10.1002/jcb.28188" @default.
• W2911142703 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30614034" @default.
• W2911142703 hasPublicationYear "2019" @default.
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