Tumor regression by expression of high physiological levels of EBV latent membrane protein 1.
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.
Hsieh
Yu-Hua
YH
Graduate Institute of Basic Medical Sciences, Chang Gung University, Kwei-shan, Taoyuan, Taiwan, Republic of China.
Liu
Hao-Ping
HP
Lo
Szecheng J
SJ
Chang
Yu-sun
YS
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
D016207:Cytokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D049452:Green Fluorescent Proteins; D018664:Interleukin-12