ABSTRACT
Heat shock protein 60 (HSP60, HSPD1) is a "chaperonin" that facilitates folding of nascent proteins into proper conformations (1). It is thought to play a critical role in the assembly, folding, and transport of proteins in the mitochondria. HSP60 also interacts with nascent cellular proteins to prevent their denaturation under heat stress (2). The HSP60 gene sequence is known and is highly conserved (3). Expression of the HSP60 gene has been associated with cisplatin resistance in several preclinical model systems and in ovarian carcinoma patients (1-6); we quantitated HSP60 mRNA expression in preclinical human ovarian and bladder carcinoma models.
ABSTRACT
Heat shock protein 60 (HSP60) participates in protein assembly, folding and transport. Increased HSP60 mRNA expression is associated with cisplatin resistance in some in vitro models and with shorter survival among ovarian cancer patients. HSP60 mRNA expression was quantitated in three independent model systems by reverse-transcription PCR (A2780 human ovarian carcinoma cell line and sublines selected for cisplatin or oxaliplatin resistance in vitro and also in the UCRU-BL13 human bladder carcinoma cell line and a cisplatin-resistant subline). Increased HSP60 mRNA expression was observed in all resistant sublines (range 2.5-15 fold), correlated with relative resistance to cisplatin and oxaliplatin. No differences in HSP60 gene copy number were apparent in resistant sublines. These data provide further evidence of a strong association between in vitro resistance to platinum compounds and increased HSP60 mRNA expression.
