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Hyperphosphorylation of replication protein A in cisplatin‐resistant and ‐sensitive head and neck squamous cell carcinoma cell lines
Author(s) -
Manthey Karoline C.,
Glanzer Jason G.,
Dimitrova Diana D.,
Oakley Greg G.
Publication year - 2010
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.21234
Subject(s) - cisplatin , hyperphosphorylation , head and neck squamous cell carcinoma , cancer research , cell cycle , cell culture , cell , etoposide , oncology , cell growth , biology , medicine , microbiology and biotechnology , chemotherapy , head and neck cancer , phosphorylation , cancer , biochemistry , genetics
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. Conclusion Loss of RPA2 hyperphosphorylation occurs in HNSCC cells and may be a marker of cellular sensitivities to cisplatin and etoposide in HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010