ROLE OF DNA METHYLTRANSFERASE 1 IN PHARYNGEAL CANCER RELATED TO TREATMENT RESISTANCE

Background. The purpose of the present study was to highlight the role of DNA methyltransferase 1 (DNMT1) and its potential for improving treatment and informing prognosis for pharyngeal cancer. Methods. Human pharyngeal cancer cell lines FaDu and its derivative FaDu-C225-R were selected for cellular experiments. Furthermore, 95 pharyngeal cancer tissue specimens were analyzed by immunohistochemical staining. Results. DNMT1 was over-expressed in pharyngeal cancer specimens and cells with activated interleukin (IL)-6 signaling. When DNMT1 activity was blocked, accelerated tumor growth and treatment resistance were overcome as demonstrated by cell culture and animal experiments. The reduction in DNMT1 was associated with increased apoptosis, cell cycle arrest, and augmented irradiation-induced free radical levels and DNA damage. Furthermore, positive staining for DNMT1 in clinical cancer specimens was significantly linked to lower rates of response to treatments and shorter survival of patients with pharyngeal cancer. Conclusion. DNMT1 may be a significant clinical predictor and a potential treatment strategy against head and neck cancer. (C) 2011 Wiley Periodicals, Inc. Head Neck 33: 1132 1143, 2011