title: Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells confers chemoresistance associated with cell growth delay.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 degrees C for 1 h as well as against several cytotoxic agents, including cisplatin, staurosporin and H(2)O(2). 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 H(2)O(2), 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.
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. leejh@catholic.ac.kr
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Dongil
authors.initials: D
authors.lastname: Sun
authors.forename: Kwang-Jae
authors.initials: KJ
authors.lastname: Cho
authors.forename: Min-Sik
authors.initials: MS
authors.lastname: Kim
authors.forename: Myung-Hwa
authors.initials: MH
authors.lastname: Hong
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Kim
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins