Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line.

作者: T Tokunaga , T Tsuchida , H Kijima , K Okamoto , Y Oshika

DOI: 10.1054/BJOC.2000.1363

关键词:

摘要: Mutation of c-K-ras oncogene is an important step in progression colon cancer. We used a hammerhead ribozyme (KrasRz) against mutated K-ras gene transcripts (codon 12, GTT) to inactivate mutant function the cancer cell line SW480, harbouring gene. The β-actin promoter-driven KrasRz sequence (pHβ/KrasRz) was introduced into these cells (SW480/KrasRz), and we evaluated its effects on growth expression angiogenesis-related molecules (vascular endothelial factor thrombospondin) also estimated SW480/KrasRz. specifically efficiently cleaved mRNA but not wild-type vitro. SW480/KrasRz showed decreased rate under tissue culture conditions (P< 0.01, Dunnett’s test). xenotransplantability (XeSW480/KrasRz) significantly nude mice 0.05, Fisher’s exact Tumour volume xenografts XeSW480/KrasRz smaller than that XeSW480/DisKrasRz Gene VEGF suppressed SW480/KrasRz, while TSP1 enhanced. apoptosis-related features including nuclear condensation DNA fragmentation. These results suggested ribozyme-mediated inactivation induced suppression, apoptosis alteration angiogenic expression. © 2000 Cancer Research Campaign

参考文章(34)
Olga V. Volpert, Peter J. Polverini, Noël P. Bouck, Pauline Chou, Peter A. Steck, Sambasiva Rao, Stephanie C. Hsu, Tom Mikkelsen, Inhibition of Angiogenesis in Human Glioblastomas by Chromosome 10 Induction of Thrombospondin-1 Cancer Research. ,vol. 56, pp. 5684- 5691 ,(1996)
H Kijima, Therapeutic applications of ribozymes. Pharmacology & Therapeutics. ,vol. 68, pp. 247- 267 ,(1995) , 10.1016/0163-7258(95)02008-X
Leonidas Tsiokas, Vikas P. Sukhatme, Debabrata Mukhopadhyay, Wild-Type p53 and v-Src Exert Opposing Influences on Human Vascular Endothelial Growth Factor Gene Expression Cancer Research. ,vol. 55, pp. 6161- 6165 ,(1995)
Dieter Marmé, Karin Weindel, Georg Martiny-Baron, Bernhard Barleon, Katja Mohrs, Gerhard Siemeister, Reversion of Deregulated Expression of Vascular Endothelial Growth Factor in Human Renal Carcinoma Cells by von Hippel-Lindau Tumor Suppressor Protein Cancer Research. ,vol. 56, pp. 2299- 2301 ,(1996)
Kevin J. Scanlon, Yukinori Ohta, Hironori Ishida, Hiroshi Kijima, Tsukasa Ohkawa, Anna Kaminski, Jerry Tsai, George Horng, Mohammed Kashani‐Sabet, Oligonucleotide-mediated modulation of mammalian gene expression. The FASEB Journal. ,vol. 9, pp. 1288- 1296 ,(1995) , 10.1096/FASEBJ.9.13.7557018
W Kolch, D Marmé, G Brandner, H A Weich, A Kieser, Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene. ,vol. 9, pp. 963- 969 ,(1994)
K. J. Scanlon, L. Jiao, T. Funato, W. Wang, T. Tone, J. J. Rossi, M. Kashani-Sabet, Ribozyme-mediated cleavage of c-fos mRNA reduces gene expression of DNA synthesis enzymes and metallothionein Proceedings of the National Academy of Sciences of the United States of America. ,vol. 88, pp. 10591- 10595 ,(1991) , 10.1073/PNAS.88.23.10591
T Tokunaga, Y Oshika, Y Abe, Y Ozeki, S Sadahiro, H Kijima, T Tsuchida, H Yamazaki, Y Ueyama, N Tamaoki, M Nakamura, Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer British Journal of Cancer. ,vol. 77, pp. 998- 1002 ,(1998) , 10.1038/BJC.1998.164
Vivian Zabrenetzky, Curtis C Harris, Patricia S Steeg, David D Roberts, None, Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung and breast carcinoma cell lines. International Journal of Cancer. ,vol. 59, pp. 191- 195 ,(1994) , 10.1002/IJC.2910590209
Tetsuji Tokunaga, M. Nakamura, Yoshiro Oshika, Takashi Tsuchida, Michitake Kazuno, Yoshitaka Fukushima, Kenji Kawai, Yoshiyuki Abe, Hiroshi Kijima, Hitoshi Yamazaki, Norikazu Tamaoki, Yoshito Ueyama, Alterations in tumour suppressor gene p53 correlate with inhibition of thrombospondin-1 gene expression in colon cancer cells. Virchows Archiv. ,vol. 433, pp. 415- 418 ,(1998) , 10.1007/S004280050268