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Opis

TP53 gene mutations compromising p53 transcriptional function occur in more than 50% of human cancers, including pancreatic adenocarcinoma, and render cancer cells more resistant to conventional therapy. In the last few years, many efforts have been addressed to identify p53-reactivating molecules able to restore the wild-type transcriptionally competent conformation of the mutated proteins. In the present thesis, we show that two of these compounds, CP-31398 and RITA, can induce cell growth inhibition, apoptosis, and autophagy by activating p53/DNA binding and p53 phosphorylation (Ser15), without affecting the total amount of p53. These effects occur in both wild-type and mutant p53 (mutp53) pancreatic adenocarcinoma cell lines, whereas they are much less pronounced in normal human primary fibroblasts. Furthermore, CP-31398 and RITA regulate the axis SESN1- 2/AMPK/mTOR by inducing AMPK phosphorylation in Thr172, which has a crucial role in the autophagic response.Our results support the development of an anti-tumoral strategy based on autophagy inhibition associated to the combined treatment of p53-reactivating molecules with standard chemotherapy,for both wild-type and mutant p53

Szczegóły książki

Kategoria Książki po angielsku Medicine Medicine: general issues

• Pełny tytuł: Molecular mechanisms induced by p53 reactivating molecules
• Autor: Fiorini Claudia
• Język: Angielski
• Oprawa: Miękka
• Liczba stron: 72
• EAN: 9783639667332
• ISBN: 3639667336
• ID: 09120713
• Wydawca: Scholars' Press
• Waga: 118 g
• Wymiary: 229 × 152 × 4 mm
• Data wydania: 28. October 2014

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