Differential protein expressions induced by adenovirus-mediated p16 gene transfer into Balb/c nude mouse.
To evaluate the safety of adenovirus-mediated gene transfer, we investigated differential protein expression after transducing adenoviral vector containing the p16(INK4a) tumor suppressor gene (Ad5CMV-p16) into Balb/c nude mice. We found that adenovirus-mediated p16(INK4a) gene transfer inhibited experimental lung metastasis, and that the intratumoral injection of Ad5CMV-p16 resulted in regression of A549 cell xenografted tumors in Balb/c nude mice. We investigated changes in protein expression after intratumoral injection of Ad5CMV-p16 or Ad5CMV (10(10) plaque-forming units) into A549 cell xenografted Balb/c nude mice by two-dimensional gel electrophoresis /matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Compared with the control (serum-free medium treated tumor cells) Ad5CMV-p16 gene transfer changed the expression of 29 proteins including heterogeneous nuclear ribonucleoprotein, protein phosphatase 2, 14-3-3 zeta protein, alpha-tubulin, and glutathione-S-transferase P1. Moreover, both Ad5CMV-p16 and Ad5CMV up-regulated the expression of glutathione-S-transferase P1. In addition, Ad5CMV-p16 gene transfer did not seem to increase the expression of tumorigenicity-related protein in Balb/c nude mice. Further studies will be needed to investigate the effect of Ad5CMV-p16 on normal human cells and tissues for safety evaluation. These results suggest that the p16 gene seems to have an important role in apoptosis as well as in cell cycle arrest in non-small cell lung cancer.
Kim
Okhee
O
Divison of Genetic Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration, 5 Nokbun-dong, Eunpyung-gu, Seoul 122-704, Korea. kimkfda@kfda.go.kr
Park
Misun
M
Kang
Hoil
H
Lim
Sinae
S
Lee
Choon-Taek
CT
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary / Q000628:therapy*; D002453:Cell Cycle; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019942:Genes, p16; D015316:Genetic Therapy; D005822:Genetic Vectors; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011506:Proteins / Q000032:analysis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D011506:Proteins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496557:Gstp1 protein, mouse