Effect of distinct anticancer drugs on the phosphorylation of p53 protein at serine 46 in human MCF-7 breast cancer cells.
Roscovitine (ROSC), a potent cyclin-dependent kinase inhibitor (CDI), inactivates cyclin-dependent kinase (CDK)2 resulting in the arrest of human MCF-7 breast cancer cells in G2 phase of the cell cycle. We have recently observed a strong activation of wild-type (wt) p53 protein in human MCF-7 breast cancer cells upon treatment with ROSC implicating that upregulated p53 might additionally modulate the primary action of ROSC. ROSC stabilized wt p53 protein resulting in a marked extension of its half-life. Since ROSC exhibits low cytotoxicity, it seems to upregulate p53 protein in a way different from DNA damage. ROSC induced phosphorylation of p53 protein at serine 46. Therefore, we decided to examine whether other anticancer drugs are also able to induce phosphorylation of wt p53 protein at serine 46. Exposure of MCF-7 cells to doxorubicin (DOX) at doses inducing a strong G2 arrest resulted in a weak upregulation of p53. No site-specific phosphorylation of p53 at serine 46 was detected. These results indicate that p53 activation is dispensable for DOX-induced G2 arrest. Moreover, the pattern of p53 phosphorylation strongly depends on the type of the stimulating factor.
Wesierska-Gadek
Józefa
J
Cell Cycle Regulation Group, Department of Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8 A, A-1090 Vienna, Austria. Jozefa.Gadek-Wesierski@meduniwien.ac.at
Gueorguieva
Marieta
M
Herbacek
Irene
I
Ranftler
Carmen
C
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D011687:Purines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077546:Roscovitine; D012694:Serine; D004317:Doxorubicin