Τίτλος:
Mutant p53 enhances nuclear factor κB activation by tumor necrosis factor α in cancer cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Mutations in the p53 tumor suppressor are very frequent in human cancer. Often, such mutations lead to the constitutive overproduction of mutant p53 proteins, which may exert a cancer-promoting gain of function. We now report that cancer-associated mutant p53 can augment the induction of nuclear factor κB (NFκB) transcriptional activity in response to the cytokine tumor necrosis factor α (TNFα). Conversely, down-regulation of endogenous mutant p53 sensitizes cancer cells to the apoptotic effects of TNFα. Analysis of human head and neck tumors and lung tumors reveals a close correlation between the presence of abundant mutant p53 proteins and the constitutive activation of NFκB. Together, these findings suggest that p53 mutations may promote cancer progression by augmenting NFκB activation in the context of chronic inflammation. ©2007 American Association for Cancer Research.
Συγγραφείς:
Weisz, L.
Damalas, A.
Liontos, M.
Karakaidos, P.
Fontemaggi, G.
Maor-Aloni, R.
Kalis, M.
Levrero, M.
Strano, S.
Gorgoulis, V.G.
Rotter, V.
Blandino, G.
Oren, M.
Περιοδικό:
Current Cancer Research
Λέξεις-κλειδιά:
beta galactosidase; cytokine; immunoglobulin enhancer binding protein; protein p53; small interfering RNA; tumor necrosis factor alpha, apoptosis; article; cancer cell; cancer growth; chronic inflammation; controlled study; down regulation; gene mutation; genetic transcription; head and neck tumor; human; human cell; immunohistochemistry; lung tumor; priority journal; protein analysis; protein expression; protein induction; protein protein interaction; squamous cell carcinoma, Apoptosis; Breast Neoplasms; Cell Nucleus; Down-Regulation; Genes, p53; Humans; Lung Neoplasms; NF-kappa B; Precancerous Conditions; RNA, Small Interfering; Transcription Factor RelA; Transfection; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53
DOI:
10.1158/0008-5472.CAN-06-2425
