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Association between hsp60 messenger-RNA levels and Cisplatin resistance in human head and neck-cancer cell-lines
B Nakata1, R Barton, K Robbins
1UNIV CALIF SAN DIEGO,CTR CANC 0812,LA JOLLA,CA 92093. OSAKA CITY UNIV,SCH MED,DEPT SURG 1,OSAKA 545,JAPAN. UNIV TENNESSEE,DEPT OTOLARYNGOL HEAD & NECK SURG,MEMPHIS,TN.
Abstract:
Development of resistance to cisplatin (cDDP) is a major obstacle in the cure of many cancers. Recently, a cDNA from cDDP-resistant human ovarian carcinoma cells was identified as the mitochondrial hsp60 chaperonin. The aim of this study was to determine the changes in expression of hsp60 during selection for cDDP resistance in two head and neck cancer cell lines, UMSCC5 and UMSCC10b and whether the emergence of resistance could be correlated with the level of hsp60 expression. We have selected cDDP-resistant variants of two squamous cell carcinoma cell lines, the UMSCC5 and UMSCC10b with levels of resistance varying from 1.5 to 6-fold. Concomitant with the emergence of resistance, the basal level of hsp60 increased 2 to 3-fold. In addition, less cDDP resistance as well as lower hsp60 levels were detected in cDDP resistant variants of the UMSCC10b cell line when selected in the presence of tamoxifen, suggesting a correlation between the intrinsic level of hsp60 expression and cDDP resistance. Using linear regression analysis both UMSCC5 and UMSCC10b cell lines demonstrated a high degree of correlation with coefficients of 0.91 and 0.90, respectively. In conclusion, the expression of hsp60 was closely related to the development of cDDP resistance and could be used as a marker for the emergence of cDDP resistance.
Insights
Cisplatin resistance in head and neck cancers correlates with increased mitochondrial heat shock protein 60 (hsp60) expression. Higher hsp60 levels indicate greater cisplatin resistance, suggesting hsp60 as a potential biomarker for treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cisplatin (cDDP) resistance is a significant challenge in cancer therapy.
- Mitochondrial heat shock protein 60 (hsp60) has been identified in cisplatin-resistant ovarian cancer cells.
Purpose of the Study:
- To investigate hsp60 expression changes during cisplatin resistance development in head and neck cancer cell lines.
- To determine if hsp60 expression levels correlate with cisplatin resistance.
Main Methods:
- Selection of cisplatin-resistant variants from UMSCC5 and UMSCC10b head and neck squamous cell carcinoma lines.
- Quantification of hsp60 expression levels in resistant cell lines.
- Linear regression analysis to assess correlation between hsp60 levels and resistance.
Main Results:
- Cisplatin resistance increased 1.5 to 6-fold in selected cell lines.
- Basal hsp60 levels increased 2 to 3-fold concurrently with resistance.
- A strong positive correlation (R=0.91 for UMSCC5, R=0.90 for UMSCC10b) was found between hsp60 expression and cisplatin resistance.
Conclusions:
- hsp60 expression is closely linked to the development of cisplatin resistance in head and neck cancers.
- hsp60 can serve as a predictive biomarker for cisplatin resistance emergence.
