Damage and Cellular Stress Responses 27 Protects Adenocarcinoma Cells from UV-Induced ptosis by Akt and p21-Dependent Pathways

ownload scriptional activation of p53 target genes, due to DNA damage, causes either apoptosis or survival by cell rrest and DNA repair. However, the regulators of the choice between cell death and survival signaling have en completely elucidated. Here, we report that human adenocarcinoma cells (MCF-7) survive UV-induced damage by heat shock protein 27 (Hsp27)–assisted Akt/p21 phosphorylation/translocation. Protein levels p53 target genes, such as p21, Bcl-2, p38MAPK, and Akt, showed a positive correlation to Hsp27 level 48 hours postirradiation, whereas p53 expression increased initially but started decreasing after 12 hours. prevented the G1-S phase cell cycle arrest, observed after 8 hours of post–UV irradiation, and PARP-1 e was inhibited. Conversely, silencing Hsp27 enhanced G1-S arrest and cell death. Moreover, use of either or Akt small interference RNA reduced p21 phosphorylation and enhanced its retention in nuclei even 8 hours postirradiation, resulting in enhanced cell death. Our results showed that Hsp27 expression and its chaperoning interaction increases Akt stability, and p21 phosphorylation and nuclear-to-cytoplasm transn, both essential effects for the survival of UV-induced DNA-damaged cells. We conclude that the role of locatio Hsp27 in cancer is not only for enhanced p53 proteolysis per se, rather it is also a critical determinant in p21 phosphorylation and translocation. Mol Cancer Res; 8(10); 1399–412. ©2010 AACR.