title: REG Iα activates c-Jun through MAPK pathways to enhance the radiosensitivity of squamous esophageal cancer cells.
abstract: 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.
authors: Department of Surgery, Graduate School of Medicine, Akita University, Akita, Japan.
authors: Akiyuki
authors: A
authors: Wakita
authors: Satoru
authors: S
authors: Motoyama
authors: Yusuke
authors: Y
authors: Sato
authors: Souichi
authors: S
authors: Koyota
authors: Shuetsu
authors: S
authors: Usami
authors: Kei
authors: K
authors: Yoshino
authors: Tomohiko
authors: T
authors: Sasaki
authors: Kazuhiro
authors: K
authors: Imai
authors: Hajime
authors: H
authors: Saito
authors: Yoshihiro
authors: Y
authors: Minamiya
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D051847:Lithostathine / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000235:genetics
chemical_list: D051847:Lithostathine; D016755:Proto-Oncogene Proteins c-jun; C497617:REG1A protein, human; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases
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