Oropharyngeal Carcinomas Harboring HPV‐E6 Display Resistance to Liberation of P53 and Sensitivity to Oxidative Stress. (2nd September 2014)

• Record Type: Journal Article
• Authors: Lau, Andrew S.; Jones, Terence M.; Boyd, Mark T.
• Is Part Of: Otolaryngology--head and neck surgery. Volume 151(2014)Supplement 1
• Page Start: P174
• Page End: P174
• Publication Date: 2014-09-02
• Subjects: Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599814541629a116
• Languages: English
• ISSNs: 0194-5998

Abstract

Abstract : Objectives: Analyze the effect of (1) Nutlin‐3, a small molecule liberator of p53, on human papillomavirus (HPV) E6 protein‐driven oropharyngeal squamous cell carcinoma (OPSCC) cell lines and (2) the response of such cell lines to oxidative stress. Methods: Reproducible drug sensitivity (MTT) and clonogenic assays were performed, with treatments with Nutlin‐3 and hydrogen peroxide. Western blots were performed for p53 and MDM2 expression. Results: Our data show that UM‐SCC‐47, an oropharyngeal cancer cell line harboring HPV E6, displays no growth or radiation sensitivity to Nutlin‐3. As expected from previous work UM‐SCC‐74A, an oropharyngeal cancer cell line not driven by HPV and harboring wild‐type p53, displayed both growth and radiation sensitivity. Similarly, UM‐SCC‐4, an oropharyngeal cancer cell line not driven by HPV but harboring mutant p53, displayed minimal growth or radiation sensitivity. Early results show that UM‐SCC‐47 displays significantly greater sensitivity to oxidative stress than cell lines negative for HPV and harboring wild‐type p53. Conclusions: We have shown for the first time that Nutlin‐3 has no effect in cells expressing HPV E6. We have also shown that p53‐deficient cells have an impaired response to oxidative stress. Such impaired regulation of oxidative stress and metabolism could be exploited in a number of different ways and may have implications for the targeting of cancers that have mutant or no p53, which typically carry a worse prognosis.