title: Glucose regulated protein 78 (GRP78) inhibits apoptosis and attentinutes chemosensitivity of gemcitabine in breast cancer cell via AKT/mitochondrial apoptotic pathway.
abstract: The underlying mechanism of gemcitabine resistance during breast cancer treatment remains unclear. Glucose regulated protein 78 (GRP78) frequently triggered by anticancer agents, was substantially elevated in gemcitabine resistant sublines. Ectopic expression of GRP78 changes gemcitabine chemosensitivity and apoptosis levels in breast cancer cells. Further experiments showed an involvement of caspase 9, not caspase 8, in gemcitabine resistance and GRP78-mediated chemosensitivity, suggesting that mitochondria apoptotic pathway was activated by GRP78. This finding was further supported by the observations of AKT activation, Bcl-2 increase, Bax and Bim decrease. Conclusively, GRP78 plays a vital role in gemcitabine resistance and clinical strategy to improve gemcitabine efficacy in breast cancer by manipulating GRP78 should be explored.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Tao
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
authors.forename: Zheng-Hua
authors.initials: ZH
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China. Electronic address: huxc16@gmail.com.
authors.forename: Xi-Chun
authors.initials: XC
authors.lastname: Hu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D003841:Deoxycytidine; D051057:Proto-Oncogene Proteins c-akt; D000093542:Gemcitabine
keywords: Apoptosis; Breast cancer; GRP78; Gemcitabine resistance