Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference

作者: H Sumimoto , S Yamagata , A Shimizu , H Miyoshi , H Mizuguchi

DOI: 10.1038/SJ.GT.3302391

关键词:

摘要: Increase of Skp-2, which is involved in the degradation cell cycle regulators including p27Kip1, p21 and c-myc, one important mechanisms for dysregulation cycles various cancers. We applied RNA interference (RNAi) Skp-2 by using HIV-lentiviral or adenoviral vectors a human small-cell lung carcinoma line with increased to evaluate RNAi strategy cancer gene therapy. HIV-lentivirus-mediated resulted efficient inhibition vitro growth cells through increase p27Kip1 p21, but no significant effect on without high expression. Furthermore, intratumoral administration adenovirus siRNA vector efficiently inhibited established subcutaneous tumor NOD/SCID mice. These results indicate that may be useful therapy cancers

参考文章(19)
Matthew L. Fero, Erin Randel, Kay E. Gurley, James M. Roberts, Christopher J. Kemp, The murine gene p27Kip1 is haplo-insufficient for tumour suppression Nature. ,vol. 396, pp. 177- 180 ,(1998) , 10.1038/24179
Hedwig Sutterlüty, Eric Chatelain, Alain Marti, Christiane Wirbelauer, Matthias Senften, Uli Müller, Wilhelm Krek, None, p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nature Cell Biology. ,vol. 1, pp. 207- 214 ,(1999) , 10.1038/12027
So Young Kim, Andreas Herbst, Kathryn A Tworkowski, Simone E Salghetti, William P Tansey, Skp2 Regulates Myc Protein Stability and Activity Molecular Cell. ,vol. 11, pp. 1177- 1188 ,(2003) , 10.1016/S1097-2765(03)00173-4
Makoto Miyagishi, Hidetoshi Sumimoto, Hiroyuki Miyoshi, Yutaka Kawakami, Kazunari Taira, Optimization of an siRNA‐expression system with an improved hairpin and its significant suppressive effects in mammalian cells Journal of Gene Medicine. ,vol. 6, pp. 715- 723 ,(2004) , 10.1002/JGM.556
Roger A Greenberg, Rónán C O'Hagan, Hongyu Deng, Qiurong Xiao, Steven R Hann, Robert R Adams, Serge Lichtsteiner, Lynda Chin, Gregg B Morin, Ronald A DePinho, Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation Oncogene. ,vol. 18, pp. 1219- 1226 ,(1999) , 10.1038/SJ.ONC.1202669
E. Latres, R. Chiarle, B. A. Schulman, N. P. Pavletich, A. Pellicer, G. Inghirami, M. Pagano, Role of the F-box protein Skp2 in lymphomagenesis. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 98, pp. 2515- 2520 ,(2001) , 10.1073/PNAS.041475098
Hiroyuki Mizuguchi, Mark A. Kay, Efficient construction of a recombinant adenovirus vector by an improved in vitro ligation method Human Gene Therapy. ,vol. 9, pp. 2577- 2583 ,(1998) , 10.1089/HUM.1998.9.17-2577
M. Gstaiger, R. Jordan, M. Lim, C. Catzavelos, J. Mestan, J. Slingerland, W. Krek, Skp2 is oncogenic and overexpressed in human cancers Proceedings of the National Academy of Sciences of the United States of America. ,vol. 98, pp. 5043- 5048 ,(2001) , 10.1073/PNAS.081474898
Hidetoshi Sumimoto, Makoto Miyagishi, Hiroyuki Miyoshi, Shizuko Yamagata, Ayako Shimizu, Kazunari Taira, Yutaka Kawakami, Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interference Oncogene. ,vol. 23, pp. 6031- 6039 ,(2004) , 10.1038/SJ.ONC.1207812
Sana Yokoi, Kohichiroh Yasui, Toshihiko lizasa, Takashi Takahashi, Takehiko Fujisawa, Johji Inazawa, Down-regulation of SKP2 induces apoptosis in lung-cancer cells. Cancer Science. ,vol. 94, pp. 344- 349 ,(2003) , 10.1111/J.1349-7006.2003.TB01444.X