Hyperphosphorylation of replication protein A in cisplatin-resistant and -sensitive head and neck squamous cell carcinoma cell lines

Head Neck. 2010 May;32(5):636-45. doi: 10.1002/hed.21234.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Etoposide / pharmacology*
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / pathology
  • Humans
  • Phosphorylation
  • Replication Protein A / metabolism*


  • Antineoplastic Agents
  • Replication Protein A
  • Etoposide
  • Cisplatin