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Involvement of Heat Shock Proteins in Protection of Tumor Cells from Genotoxic Stresses

  • Chapter
Heat Shock Proteins in Cancer

Part of the book series: Heat Shock Proteins ((HESP,volume 2))

Abstract

Anti-apoptotic functions of heat shock proteins Hsp70 and Hsp27 are well established. However, radiation and genotoxic antineoplastic drugs at clinically relevant doses induce apoptosis mostly in lymphoid cells, while in epithelial tumors they evoke different type of response, mainly senescence and mitotic catastrophe, which leads to loss of clonogenic potential of cells. Here we review old and new data showing that upregulation of Hsp27 or Hsp70 levels protect various tumor cell lines from gamma- and UV-radiation and genotoxic anti-neoplastic drugs. Accordingly, downregulation of Hsp27 or Hsp70 levels by antisense or siRNA sensitizes tumor cells to these agents. Importantly, protection and sensitization by modulation of Hsp27 or Hsp70 levels were manifested not only by modulation of apoptosis, but by clonogenic survival as well, and recent data indicate that these Hsps can suppress also drug-induced senescence. Several studies demonstrated that intrinsic and acquired chemo- and radioresistance in tumor cell lines and in patients with certain forms of cancers can be associated with upregulation of Hsp27 and/or Hsp70. Possible mechanisms of Hsp-induced protection, in particular, modulation of p53-dependent and p53-independent DNA-damaging signaling pathways, are discussed

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Authors and Affiliations

  1. Boston University Medical School, Boston, MA 02118, USA

    Cornelia O’Callaghan-Sunol & Vladimir L. Gabai

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  1. Cornelia O’Callaghan-Sunol
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  2. Vladimir L. Gabai
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Editors and Affiliations

  1. Harvard Medical School, Boston, U.S.A

    Stuart K. Calderwood

  2. Boston University School of Medicine, Boston, U.S.A

    Michael Y. Sherman

  3. National Research Council CONICET, Mendoza, Argentina

    Daniel R. Ciocca

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© 2007 Springer

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O’Callaghan-Sunol, C., Gabai, V.L. (2007). Involvement of Heat Shock Proteins in Protection of Tumor Cells from Genotoxic Stresses. In: Calderwood, S.K., Sherman, M.Y., Ciocca, D.R. (eds) Heat Shock Proteins in Cancer. Heat Shock Proteins, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6401-2_9

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