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: Akiyuki Wakita, Satoru Motoyama, Yusuke Sato, Souichi Koyota, Shuetsu Usami, Kei Yoshino, Tomohiko Sasaki, Kazuhiro Imai, Hajime Saito, Yoshihiro Minamiya
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 7 Pg. 5249-54 (Jul 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25656613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lithostathine
• Proto-Oncogene Proteins c-jun
• REG1A protein, human
• RNA, Messenger
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases

Topics

• Carcinoma, Squamous Cell (genetics, pathology, radiotherapy)
• Cell Line, Tumor
• Esophageal Neoplasms (genetics, pathology, radiotherapy)
• Esophageal Squamous Cell Carcinoma
• Gene Expression Regulation, Neoplastic
• Humans
• JNK Mitogen-Activated Protein Kinases (biosynthesis, genetics)
• Lithostathine (genetics, metabolism)
• MAP Kinase Signaling System (genetics)
• Mitogen-Activated Protein Kinases (genetics)
• Proto-Oncogene Proteins c-jun (biosynthesis, genetics)
• RNA, Messenger (biosynthesis)
• Radiation Tolerance (genetics)