Overexpression of the 27 KDa heat shock protein is associated with thermoresistance and chemoresistance but not with radioresistance.
OBJECTIVE
The heat shock protein (hsp27) correlates with thermotolerance and chemoresistance. Our main objective was to assess the response to radiotherapy both in vitro and in vivo in correlation with various concentrations of hsp27. The second objective was to evaluate the relation between hsp27 and glutathione-s-transferase pi (GST pi).


METHODS
For the in vitro study, thermoresistant cell lines, expressing various amounts of hsp27, were used to assess the role of this protein in radioresistance. To verify the efficiency of hsp27 in these cells lines to confer resistance to cytotoxic agents, these cells were also treated with heat shock and cisplatin. Furthermore, the role of hsp27 expression 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 potentially 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 confirmed to increased the cellular resistance to heat and to cisplatinum. In vivo, we showed that overexpression of various amounts of hsp27 did not correlate with local control of the tumor. In vivo, hsp27 was only significantly associated with GST pi. Expression of GST pi was associated with poor local (p = 0.01) control and survival (p = 0.08) in a Cox model.


CONCLUSIONS
It is concluded that the mechanisms responsible for hsp27-mediated heat and drug resistance are not involved in radioprotection.
Fortin
A
A
Department of Radiation Oncology, de l'Université Laval, Québec, Canada. afortin@viedeotron.ca
Raybaud-Diogène
H
H
Têtu
B
B
Deschenes
R
R
Huot
J
J
Landry
J
J
D000818:Animals; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy; D002460:Cell Line / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics; D011853:Radiobiology; D014162:Transfection / Q000379:methods
D015415:Biomarkers; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D005982:Glutathione Transferase