Thyroid
tumors are the most common types of endocrine
malignancies and are commonly treated with radioactive
iodine (RAI) to destroy remaining
cancer cells following surgical intervention. We previously reported that the expression levels of
double-stranded DNA-dependent
protein kinase catalytic subunit (
DNA-
PKcs), which plays a key role in non-homologous end joining, are correlated with the radiosensitivity of
cancer cells. Specifically, cells expressing high levels of
DNA-
PKcs exhibited radiation resistance, whereas cells expressing low levels were sensitive to
radiation treatment. In this study, we observed full-length native
DNA-
PKcs (460 kDa) in radiation-resistant FRO and KTC-2 cells through western blot analysis using an antibody against the C-terminus of
DNA-
PKcs. In contrast, cleaved
DNA-
PKcs (175 kDa) were observed in radiation-sensitive TPC-1 and KTC-1 cells. Almost equal amounts of
DNA-
PKcs were observed in moderately radiation-sensitive WRO cells. We also describe a simple method for the prediction of
radiation therapy efficacy in individual cases of
thyroid cancers based on staining for
DNA-
PKcs in human
cancer cell lines. Immunofluorescent staining showed that native
DNA-
PKcs was localized largely in the cytoplasm and only rarely localized in the nuclei of radiation-resistant
thyroid cancer cells, whereas in radiation-sensitive
cancer cells a 175-kDa cleaved C-terminal fragment of
DNA-
PKcs was localized mainly inside the nuclei. Therefore,
DNA-
PKcs moved to the nucleus after γ-ray irradiation. Our results suggest a new method for classifying human thyroid
tumors based on their cellular distribution patterns of
DNA-
PKcs in combination with their radiosensitivity.