title: Overexpression of beclin1 induced autophagy and apoptosis in lungs of K-rasLA1 mice.
abstract: Beclin1, as a key molecule in controlling autophagy pathway, can activate both cell survival and cell death pathway. As a role of autophagy in cancer progression remains controversial, introduction of beclin1 to the lungs of K-ras(LA1) mice was performed via inhalation. Prolonged autophagy activation was induced by repeated exposure of lentivirus-beclin1, total of 8 times (2 times/week, 4 weeks). By the time of sacrifice, lungs were collected and analyzed for the therapeutic efficacy. Total numbers of tumors on the surface and histopathological tumor progression were reduced in the lungs of K-ras(LA1) mice. Successful delivery of beclin1 induced autophagy and apoptosis in the target organ, which were confirmed by following features; increased autophagic vacuoles in the cytosol, increased number of mitochondria with decreased mitochondrial 12S RNA, and increased protein levels of mitochondria-related apoptosis. Markers for cell proliferation and angiogenesis, PCNA and VEGF, which used for prediction of cancer prognosis, were significantly reduced after introduction of beclin1. Taken together, the results indicate that autophagy regulating gene, beclin1, can be a potential target for lung cancer gene therapy.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Bitna
authors.initials: B
authors.lastname: Kang
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea; Graduate School of Convergence Science and Technology, Seoul National University, Suwon 443-270, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Republic of Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1; D049109:Cell Proliferation; D015870:Gene Expression; D011905:Genes, ras; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009389:Neovascularization, Pathologic; D014161:Transduction, Genetic; D047368:Tumor Burden / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse
keywords: Apoptosis; Autophagy; Beclin1; Gene therapy; Lung cancer; Mitochondria