MESSENGER-RNA LEVELS OF MOLECULAR CHAPERONES HSP27, HSP60 AND HSP70 IN CISPLATIN-RESISTANT SQUAMOUS-CELL CARCINOMAS

The relationship between cisplatin (cDDP) resistance and the expressio n of the molecular chaperonins hsp70, 60 and 27 was studied in two hea d 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 var iants (15th selection) of the UM-SCC-5 and UM-SCC-10b were 7.2+/-1.5 m u M and 20.1+/-1.2 mu M, and 6.5+/-0.6 mu M and 40.1+/-1.2 mu M, respe ctively. The emergence of cDDP resistance was closely related to the i ncrease 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 hsp6 0 mRNA in the cDDP resistant variants (15th selection). Expression of hsp27 was increased at higher levels of resistance in the UM-SCC-10B v ariants only (3 to 5-fold), and not in the UM-SCC-5 variants. In contr ast 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 al l slightly increased after cDDP treatment (IC70 dose). However, only h sp60 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 act ivity of hsp27 and hsp70.