Hsp27 protects adenocarcinoma cells from UV-induced apoptosis by Akt and p21-dependent pathways of survival

• Published in: Molecular cancer research Vol. 8; no. 10; pp. 1399 - 1412
• Main Authors: Kanagasabai, Ragu, Karthikeyan, Krishnamurthy, Vedam, Kaushik, Qien, Wang, Zhu, Qianzheng, Ilangovan, Govindasamy
• Format: Journal Article
• Language: English
• Published: United States 01.10.2010
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Apoptosis - physiology; Apoptosis - radiation effects; Cell Line, Tumor; Cell Survival - genetics; Cell Survival - radiation effects; Cyclin-Dependent Kinase Inhibitor p21 - physiology; Cyclin-Dependent Kinase Inhibitor p21 - radiation effects; Cytoprotection - physiology; Cytoprotection - radiation effects; DNA Damage - radiation effects; HSP27 Heat-Shock Proteins - physiology; HSP27 Heat-Shock Proteins - radiation effects; Humans; Hydrolysis - radiation effects; Phosphorylation - physiology; Phosphorylation - radiation effects; Protein Stability - radiation effects; Protein Transport - genetics; Protein Transport - radiation effects; Proto-Oncogene Proteins c-akt - physiology; Proto-Oncogene Proteins c-akt - radiation effects; Signal Transduction - genetics; Signal Transduction - radiation effects; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Protein p53 - radiation effects; Ultraviolet Rays - adverse effects
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-10-0181

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