title: Targeted expression of BikDD eliminates breast cancer with virtually no toxicity in noninvasive imaging models.
abstract: Breast cancer is a major public health problem all over the world, and the current treatment strategies are not potent enough for some patients, especially those with triple-negative breast cancer. Therefore, novel and more effective treatments are critically needed. Of the current methods, targeted therapy, which not only retains cancer-specific expression but also limits toxicity, is a new strategy for treating cancers. In this study, we found that the human telomerase reverse transcriptase (hTERT; T) promoter also possesses high target specificity in breast cancer. Moreover, we developed a versatile T-based breast cancer-specific promoter VISA (VP16-Gal4-WPRE integrated systemic amplifier) composite (T-VISA) to target transgene expression in breast tumors, which has stronger activity comparable or higher than that of the cytomegalovirus promoter in cancer cells. Thereafter, targeted expression of BikDD (a mutant form of proapoptotic gene Bik) through the T-VISA platform in breast cancer initiated robust antitumor effects and prolonged survival in multiple xenograft and syngeneic orthotopic mouse models of breast tumors with virtually no toxicity in intact mice. Thus, these findings show that our T-VISA-BikDD nanoparticles effectively and safely eradicate breast cancer in vitro and in vivo and are worthy of development in clinical trials treating breast cancer.
authors: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.
authors: Xinhua
authors: X
authors: Xie
authors: Laisheng
authors: L
authors: Li
authors: Xiangsheng
authors: X
authors: Xiao
authors: Jiaoli
authors: J
authors: Guo
authors: Yanan
authors: Y
authors: Kong
authors: Minqing
authors: M
authors: Wu
authors: Wanli
authors: W
authors: Liu
authors: Guoquan
authors: G
authors: Gao
authors: Jennifer L
authors: JL
authors: Hsu
authors: Weidong
authors: W
authors: Wei
authors: Mien-Chie
authors: MC
authors: Hung
authors: Xiaoming
authors: X
authors: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy; D006801:Humans; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D024101:Mitochondrial Proteins; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics; D019076:Transgenes; D047368:Tumor Burden
chemical_list: D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D049409:Luciferases, Firefly; C509186:TERT protein, human; D019098:Telomerase