PURPOSE: The purpose of the study is to investigate the regulation of p53 expression in response to 5-fluorouracil (5-FU) in human colon cancer cells. EXPERIMENTAL DESIGN: Human colon cancer RKO cells were used as our model system. The levels of p53 expression and p53 protein stability in response to 5-FU and doxorubicin were investigated. In addition, the acetylation and phosphorylation status of p53 after 5-FU and doxorubicin treatment was analyzed by Western immunoblot analysis. RESULTS: Treatment of human colon cancer RKO cells with 10 micromol/L 5-FU resulted in significantly increased levels of p53 protein with maximal induction observed at 24 h. The level of acetylated p53 after 5-FU exposure remained unchanged, whereas the phosphorylated form of p53 was expressed only after 24 h drug treatment. Northern blot analysis revealed no change in p53 mRNA levels after 5-FU treatment. No differences were observed in the half-life of p53 protein in control and 5-FU-treated cells, suggesting that the increase in p53 was the direct result of newly synthesized protein. In contrast, the maximal induction of p53, in response to doxorubicin, occurred at an earlier time point (4 h) when compared with cells treated with 5-FU (24 h). No corresponding change in p53 mRNA was observed. Levels of both the acetylated and phosphorylated forms of p53 were markedly increased upon doxorubicin exposure when compared with treatment with 5-FU, resulting in a significantly prolonged half-life of p53 (120 versus 20 min). CONCLUSION: These results, taken together, suggest that the regulatory mechanisms controlling p53 expression, in response to a cellular stress, are complex and are dependent upon the specific genotoxic agent. With regard to 5-FU, we show that translational regulation is an important process for controlling p53 expression. Studies are under way to define the specific mechanism(s) that control 5-FU-mediated translational regulation of p53.
PURPOSE: The purpose of the study is to investigate the regulation of p53 expression in response to 5-fluorouracil (5-FU) in humancolon cancer cells. EXPERIMENTAL DESIGN:Humancolon cancer RKO cells were used as our model system. The levels of p53 expression and p53 protein stability in response to 5-FU and doxorubicin were investigated. In addition, the acetylation and phosphorylation status of p53 after 5-FU and doxorubicin treatment was analyzed by Western immunoblot analysis. RESULTS: Treatment of humancolon cancer RKO cells with 10 micromol/L 5-FU resulted in significantly increased levels of p53 protein with maximal induction observed at 24 h. The level of acetylated p53 after 5-FU exposure remained unchanged, whereas the phosphorylated form of p53 was expressed only after 24 h drug treatment. Northern blot analysis revealed no change in p53 mRNA levels after 5-FU treatment. No differences were observed in the half-life of p53 protein in control and 5-FU-treated cells, suggesting that the increase in p53 was the direct result of newly synthesized protein. In contrast, the maximal induction of p53, in response to doxorubicin, occurred at an earlier time point (4 h) when compared with cells treated with 5-FU (24 h). No corresponding change in p53 mRNA was observed. Levels of both the acetylated and phosphorylated forms of p53 were markedly increased upon doxorubicin exposure when compared with treatment with 5-FU, resulting in a significantly prolonged half-life of p53 (120 versus 20 min). CONCLUSION: These results, taken together, suggest that the regulatory mechanisms controlling p53 expression, in response to a cellular stress, are complex and are dependent upon the specific genotoxic agent. With regard to 5-FU, we show that translational regulation is an important process for controlling p53 expression. Studies are under way to define the specific mechanism(s) that control 5-FU-mediated translational regulation of p53.
Authors: Julie Pariseau; Patricia McKenna; Mohammed Aboelkhair; Richard Saint-Louis; Emilien Pelletier; T Jeffrey Davidson; Réjean Tremblay; Franck C J Berthe; Ahmed Siah Journal: Ecotoxicology Date: 2011-06-18 Impact factor: 2.823
Authors: Susan M Christner; Dana M Clausen; Jan H Beumer; Robert A Parise; Jianxia Guo; Yijun Huang; Alexander S Dömling; Julie L Eiseman Journal: Cancer Chemother Pharmacol Date: 2015-06-07 Impact factor: 3.333
Authors: Chunwan Lu; John D Klement; Dafeng Yang; Thomas Albers; Iryna O Lebedyeva; Jennifer L Waller; Kebin Liu Journal: Cancer Lett Date: 2020-02-12 Impact factor: 8.679
Authors: Yari Ciribilli; Virginia Andreotti; Daniel Menendez; Jan-Stephan Langen; Gilbert Schoenfelder; Michael A Resnick; Alberto Inga Journal: PLoS One Date: 2010-04-21 Impact factor: 3.240