Abstract 1409: p53 negatively regulates keratin 17 expression in oral squamous cell carcinoma

Abstract

Abstract Background: Cytokeratin 17 (K17) has been shown to promote tumorigenesis and aggressiveness in oral squamous cell carcinomas (OSCCs) and other various carcinomas. Although p53 reportedly induces K17 transcription by irradiation, the correlation between p53 and K17 in OSCCs remains unknown. Methods: Human OSCC cell lines SAS and Ca9-22 were examined by Western blot, immunohistochemistry, ChIP assays, and overexpression of wild-type p53. Biopsy specimens from patients with OSCC were used for immunohistochemistry.Results: Western blot and immunohistochemistry showed that K17 expression negatively correlated with p53 expression. In biopsy specimens, positive staining for K17 was observed in OSCC cells that were negative for p53 in a mutually exclusive manner. SAS cells, which have higher K17 expression and almost negative p53 expression, showed more aggressive characteristics than Ca9-22 cells. A mutation to cause a premature stop codon was identified in the TP53 gene in SAS cells by DNA sequencing, whereas no mutation in the TP53 gene was identified in Ca9-22 cells. In addition, ChIP analysis showed that p53 bound specifically to the promoter region of the K17 gene. Furthermore, overexpression of wild-type p53 suppressed K17 expression in SAS cells. Conclusion: p53 acts as a direct transcriptional repressor of K17 in OSCCs. The interaction between p53 and K17 may regulate aggressiveness of the carcinoma cells. Citation Format: Mayu Enaka, Masako Nakanishi, Yasuteru Muragaki. p53 negatively regulates keratin 17 expression in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1409.