Overexpression of the 27 kDa heat shock protein is associated with thermoresistance and chemoresistance but not with radioresistance

Purpose: The heat shock protein (hsp27) correlates with thermotolerance and chemoresistance, Our main objective was to assess the response to radiothe rapy both in vitro and in vivo in correlation with various concentrations o f hsp27, The second objective was to evaluate the relation between hsp27 an d glutathione-s-transferase pi (GST pi) Methods and Materials: For the in vitro study, thermoresistant cell lines, expressing various amounts of hsp27, were used to assess the role of this p rotein in radioresistance, To verify the efficiency of hsp27 in these cells lines to confer resistance to cytotoxic agents, these cells were also trea ted with heat shock and cisplatin, Furthermore, the role of hsp27 expressio n was studied in vivo by immunochemistry in 98 patients with head and neck squamous cell carcinoma treated by radiotherapy. hsp27 was correlated with local control of the tumor and with clinical and biologic factors potential ly able to affect the local control, including p53, ki-67, ploidy, and GST, Results: In vitro, high constitutive levels of expression of hsp27 did not significantly influence the survival curves of transfected cells exposed to radiation as compared to control cells although hsp27 overexpression was c onfirmed to increased the cellular resistance to heat and to cisplatinum. I n vivo, we showed that overexpression of various amounts of hsp27 did not c orrelate with local control of the tumor, In who, hsp27 was only significan tly associated with GST pi. Expression of GST pi was associated with poor l ocal (p = 0.01) control and survival (p = 0.08) in a Cox model. Conclusions: It is concluded that the mechanisms responsible for hsp27-medi ated heat and drug resistance are not involved in radioprotection. (C) 2000 Elsevier Science Inc.