title: Development of PEA-15 using a potent non-viral vector for therapeutic application in breast cancer.
abstract: Advanced breast cancer requires systemic treatment, therefore developing an efficient and safe strategy is urgently needed. To ensure the success of target therapy, we have developed a breast cancer-specific construct (T-VISA) composed of the human telomerase reverse transcriptase (hTERT; T) promoter and a versatile transgene amplification vector VISA (VP16-GAL4-WPRE integrated systemic amplifier) to target PEA-15 (phosphoprotein enriched in astrocytes) in advanced breast tumors. PEA-15 contains a death effector domain that sequesters extracellular signal-regulated kinase (ERK) in the cytoplasm, thereby inhibiting cell proliferation and inducing apoptosis. T-VISA-PEA-15 was found to be highly specific, selectively express PEA-15 in breast cancer cells, and induce cancer-cell killing in vitro and in vivo without affecting normal cells. Moreover, intravenous treatment with T-VISA-PEA-15 coupled with liposome nanoparticles attenuated tumor growth and prolonged survival in mice bearing advanced breast tumors. Importantly, there was virtually no severe toxicity when PEA-15 is expressed by our T-VISA system compared with cytomegalovirus (CMV) promoter. Thus, our findings demonstrate an effective cancer-targeted therapy that is worthy of development in clinical trials eradicating advanced breast cancer.
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.lastname: Pengliu
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Minqing
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wei
authors.affiliation: Section of Translational Breast Cancer Research, Departments of Breast Medical Oncology and Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jangsoon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Section of Translational Breast Cancer Research, Departments of Breast Medical Oncology and Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chandra
authors.initials: C
authors.lastname: Bartholomeusz
authors.affiliation: Section of Translational Breast Cancer Research, Departments of Breast Medical Oncology and Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Peopley's Republic of China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D019076:Transgenes / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; C509186:TERT protein, human; D019098:Telomerase
keywords: Breast cancer; PEA-15; T-VISA system; Target therapy