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Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells confers chemoresistance associated with cell growth delay

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Abstract

Purpose

Among the family of heat shock proteins (HSPs), HSP70 and HSP27 have been implicated in tumorigenesis and chemoresistance, probably via the prevention of apoptosis. HSP27 levels are frequently increased in large populations of tumors of the head and neck, but the mechanism of its chemoresistance is not yet fully understood. In the present study, the role of HSP27 in the resistance to cytotoxic stress was studied in Hep-2 human laryngeal cancer cells.

Method

We established a Hep-2 cell line overexpressing HSP27 and examined whether the expression of HSP27 provides resistance to heat shock and several cytotoxic agents using a MTT colorimetic assay. Cell cycle progression was assessed by flow cytometry and fluorescence staining was performed for F-actin filaments.

Results

HSP27 overexpression induced cellular resistance to heat shock at 45°C for 1 h as well as against several cytotoxic agents, including cisplatin, staurosporin and H2O2. However, no difference in sensitivity to irradiation or serum starvation was found. Moreover, HSP27 overexpressing Hep-2 cells showed a delayed cell growth, compared to control cells. To determine if the decreased cell proliferation in HSP27 overexpressing cells contributed to chemoresistance, control Hep-2 cells were synchronized at the late G1 phase by treatment with mimosine. The synchronized Hep-2 cells were resistant to cisplatin and H2O2, but not to irradiation or serum starvation, correlating the protection effect shown in HSP27 overexpressing cells. These results suggest that the overexpression of HSP27 in Hep-2 cells confers chemoresistance which is associated with the delay in cell growth. We also propose that the stabilization of F-actin observed in Hep-2/hsp27 cells is partly related to the delay in cell cycle progression, by showing that the induction of actin polymerization in Hep-2/neo cells results in the retardation of cell growth as well as a cytoprotective effect as observed in Hep-2/hsp27.

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Acknowledgments

This work was supported, in part, by grants from the alumni associated of the Department of Otolaryngology Head and Neck Surgery, The Catholic University of Korea.

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Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-Gu, Seoul, 137-701, South Korea

    Jung-Hee Lee, In-Kyung Kim & Jeong-Hwa Lee

  2. Department of Otolaryngology, Head and Neck Surgery, The Catholic University of Korea, College of Medicine, Seoul, 137-701, South Korea

    Dongil Sun, Kwang-Jae Cho, Min-Sik Kim & Myung-Hwa Hong

  3. Laboratory of Functional Genomics, Korea Institute of Radiological and Medical Sciences, Seoul, 139 -706, South Korea

    Jae-Seon Lee

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  1. Jung-Hee Lee
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  2. Dongil Sun
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Correspondence to Jeong-Hwa Lee.

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Jung-Hee Lee and Dongil Sun have contributed equally to this work.

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Lee, JH., Sun, D., Cho, KJ. et al. Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells confers chemoresistance associated with cell growth delay. J Cancer Res Clin Oncol 133, 37–46 (2007). https://doi.org/10.1007/s00432-006-0143-3

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  • DOI: https://doi.org/10.1007/s00432-006-0143-3

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