title: Involvement of UTR-dependent gene expression in the maintenance of cancer stem cell like phenotypes.
abstract: The present study demonstrated the acquisition of additional malignant characteristics in irradiated mouse fibrosarcoma cells compared with the parent cells. Several reporter assays indicated that hypoxia-inducible factor (HIF)-1α, activator protein-1 and Ets-dependent transcription were activated in irradiated cells. Thecis-elements in the 5'-untranslated region (UTR) of these transcription factors plays a major role in their expression in surviving irradiated cancer cells. By contrast, there were no evident differences between the 3'-UTR-dependent repression demonstrated by parent cells and irradiated cells. A small population of parental fibrosarcoma cells was also found to exhibit the same enhanced 5'-UTR-dependent HIF-1α expression as that demonstrated by irradiated cells. These observations may indicate that high-dose X-ray irradiation affects the majority of proliferating cancer cells, but not the cancer stem cells (CSCs), and an increased CSC population may explain the progressive phenotypes of the irradiated cells. It appears likely that the transcription factors that maintain stemness are regulated by the same 5'-UTR-dependent mechanism.
authors.affiliation: Department of Oral Pathobiology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido 060-8586, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Oral Pathobiology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido 060-8586, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hatanaka
authors.affiliation: Department of Radiology and Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
authors.affiliation: Department of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishioka
keywords: Ets2; c-fos; cancer stem cell; hypoxia-inducible factor-1α; radio-resistance; repopulation; untranslated region