Hyperphosphorylation of replication protein A in cisplatin-resistant and -sensitive head and neck squamous cell carcinoma cell lines.
BACKGROUND
Resistance to chemotherapy is a major limitation in the treatment of head and neck squamous cell carcinomas (HNSCCs), accounting for high mortality rates in patients. Here, we investigated the role of replication protein A (RPA) in cisplatin and etoposide resistance.


METHODS
We used 6 parental HNSCC cell lines. We also generated 1 cisplatin-resistant progeny subline from a parental cisplatin-sensitive cell line, to examine cisplatin resistance and sensitivity with respect to RPA2 hyperphosphorylation and cell-cycle response.


RESULTS
Cisplatin-resistant HNSCC cell levels of hyperphosphorylated RPA2 in response to cisplatin were 80% to 90% greater compared with cisplatin-sensitive cell lines. RPA2 hyperphosphorylation could be induced in the cisplatin-resistant HNSCC subline. The absence of RPA2 hyperphosphorylation correlated with a defect in cell-cycle progression and cell survival.


CONCLUSIONS
Loss of RPA2 hyperphosphorylation occurs in HNSCC cells and may be a marker of cellular sensitivities to cisplatin and etoposide in HNSCC.
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska, USA.
Karoline C
KC
Manthey
Jason G
JG
Glanzer
Diana D
DD
Dimitrova
Greg G
GG
Oakley
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D010766:Phosphorylation; D051716:Replication Protein A / Q000378:metabolism*
D000970:Antineoplastic Agents; D051716:Replication Protein A; D005047:Etoposide; D002945:Cisplatin