REG Iα activates c-Jun through MAPK pathways to enhance the radiosensitivity of squamous esophageal cancer cells
- 177 Downloads
Identification of the key molecules that mediate susceptibility to anticancer treatments would be highly desirable. Based on clinical and cell biological studies, we recently proposed that regenerating gene (REG) Iα may be such a molecule. In the present study, we hypothesized that REG Iα increases radiosensitivity through activation of mitogen-activated protein kinase (MAPK) pathways. To test that idea, we transfected TE-5 and TE-9 squamous esophageal cancer cells with REG Iα and examined its involvement in MAPK signaling and its effect on susceptibility to radiotherapy. We found that REG Iα-expressing cells showed increased expression of c-Jun messenger RNA (mRNA) and phospho-c-Jun protein mediated via the c-Jun N-terminal kinase (JNK) pathway and extracellular signal-regulated kinase (ERK) pathway, as well as increased radiosensitivity. Immunohistochemical analysis confirmed the activation of c-Jun in tumors expressing REG Iα. Collectively, these findings suggest that REG Iα activates c-Jun via the JNK and ERK pathway, thereby enhancing radiosensitivity.
KeywordsREG I MAPK Radiosensitivity c-Jun JNK ERK
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture.
- 12.Motoyama S, Sugiyama T, Ueno Y, Okamoto H, Takasawa S, Nanjo H, et al. REG I expression predicts long-term survival among locally advanced thoracic squamous cell esophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy. Ann Surg Oncol. 2006;13:1724–31.CrossRefPubMedGoogle Scholar
- 16.Plotnikov A, Zehorai E, Procaccia S, Seger R. The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Biochim Biophys Acta. 1813;2011:1619–33.Google Scholar