title: Tumor regression by expression of high physiological levels of EBV latent membrane protein 1.
abstract: Induction of apoptosis in tumor cells is one of therapeutic strategies of cancer. Previous studies indicate that LMP-1 can act as governor of cell proliferation because overexpression of latent membrane protein 1 (LMP-1) of Epstein-Barr virus (EBV) inhibits cell proliferation. Here we demonstrate that overexpression of the NLMP-1, isolated from an EBV strain prominent in Taiwanese population, also possess the ability to induce apoptosis of cells, and inhibit CT-26 tumor growth in mice. Mapping studies indicate that NLMP-1 transmembrane domain is required for induction of cytotoxicity. Intratumoral delivery of vectors expressing NLMP-1 or its membrane domain via electroporation induces tumor tissue damage, suppresses tumor growth in mice, and prolongs the survival of treated animals. In addition, the membrane domain of NLMP-1 alone induces effects similar to those induced by cotreatment with NLMP-1 and IL-12. Tumor-free mice at 120 days after the initial treatments were further challenged with CT-26 tumor cells. No tumor growth was observed. Thus, NLMP-1, and more specifically the transmembrane domain of NLMP-1, may be promising new therapeutic agents for control of tumor growth.
authors.affiliation: Graduate Institute of Basic Medical Sciences, Chang Gung University, Kwei-shan, Taoyuan, Taiwan, Republic of China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Hao-Ping
authors.initials: HP
authors.lastname: Liu
authors.forename: Szecheng J
authors.initials: SJ
authors.lastname: Lo
authors.forename: Yu-sun
authors.initials: YS
authors.lastname: Chang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism / Q000627:therapeutic use; D018274:Electroporation; D005260:Female; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D018664:Interleukin-12 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D017434:Protein Structure, Tertiary; D014162:Transfection; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D049452:Green Fluorescent Proteins; D018664:Interleukin-12