title: Different Roles of CHOP and JNK in Mediating Radiation-Induced Autophagy and Apoptosis in Breast Cancer Cells.
abstract: Unfolded protein response (UPR) is comprised of complex and conserved stress pathways that function as a short-term adaptive mechanism to reduce levels of unfolded or misfolded proteins and maintain homeostasis in the endoplasmic reticulum (ER). UPR can be triggered by prolonged or persistent ER stress under many physiological or pathological conditions, including radiation exposure. Radiation-induced ER stress elicits autophagy and apoptosis in cancer cells, where C/EBP homologous protein (CHOP) and c-Jun NH2-terminal kinase (JNK) may play crucial roles. However, the specific mechanisms that regulate autophagy and apoptosis through CHOP and JNK after radiation exposure and how the balance of these activities determines the cellular radiosensitivity remain largely unclear. In this study, we found that exposure to X-ray radiation induced ER stress, UPR and high expression of CHOP and JNK. Furthermore, autophagy and apoptosis occurred in sequential order when breast cancer MDA-MB-231 and MCF-7 cells were exposed to X-ray radiation. CHOP gene knockdown with RNA interference inhibited autophagy and enhanced radiosensitivity in MDA-MB-231 cells, while impacting apoptosis and subsequently increasing radioresistance in MCF-7 cells. However, treatment with JNK inhibitor decreased autophagy while promoting apoptosis, thereby leading to radiosensitivity in both cell lines. Our results indicate that CHOP mediates radiation-induced autophagy and apoptosis in a cellular environment. Importantly, the functional consistency of regulating apoptosis and autophagy in these two irradiated breast cancer cell lines suggests that JNK may be more useful as a potential target for maximizing the efficacy of radiation therapy for breast cancers.
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.|d   University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.|d   University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zheng
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.|d   University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Liu
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.|d   University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Wu
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jin
authors.affiliation: a   Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China;|b   Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China;|c   Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; and.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress / Q000528:radiation effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D061986:MCF-7 Cells; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D047428:Protein Kinase Inhibitors; D051742:Transcription Factor CHOP; D048031:JNK Mitogen-Activated Protein Kinases