MRNA levels of molecular chaperones hsp27, hsp60 and hsp70 in cisplatin resistant squamous cell carcinomas

Abstract

The relationship between cisplatin (cDDP) resistance and the expression of the molecular chaperonins hsp70, 60 and 27 was studied in two head and neck squamous cell carcinoma cell lines (UM-SCC-5 and UM-SCC-10B). The cDDP resistant variants were obtained by continuous exposure to escalating doses of cDDP. The IC(50)s of the parent and resistant variants (15th selection) of the UM-SCC-5 and UM-SCC-10b were 7.2+/-1.5 mu M and 20.1+/-1.2 mu M, and 6.5+/-0.6 mu M and 40.1+/-1.2 mu M, respectively. The emergence of cDDP resistance was closely related to the increase in basal expression of hsp60 (r=0.85 and 0.91 for UM-SCC-5 and UM-SCC-10B, respectively) resulting in a 2 to 3-fold increase in hsp60 mRNA in the cDDP resistant variants (15th selection). Expression of hsp27 was increased at higher levels of resistance in the UM-SCC-10B variants only (3 to 5-fold), and not in the UM-SCC-5 variants. In contrast to hsp60 and hsp27, the emergence of cDDP resistance did not lead to higher hsp70 mRNA levels. In addition, we determined the ability of cDDP resistant variants to induce the hsps 27, 60 and 70 in response to cDDP treatment. In the parental cell lines, hsp27 and hsp60 were all slightly increased after cDDP treatment (IC70 dose). However, only hsp60 could be induced in the resistant variants. In summary, emergence of cDDP resistance is associated with increased levels of hsp60 mRNA in the resistant variants and an inhibition of the transcriptional activity of hsp27 and hsp70.