An anti-K-ras ribozyme suppresses oncogene expression and cell growth of human pancreatic cancer.
Hammerhead ribozymes are effective modulators of gene expression due to their simple structure, site-specific cleavage activity and catalytic potential. The K-ras oncogene is thought to play an important role in the growth of pancreatic cancer, because an activated (mutated) ras gene is found in approximately 90% of human pancreatic cancers. In this study, we designed a hammerhead ribozyme directed against K-ras mRNA at codon 25 [K-ras Rz (25)], and investigated its efficacy in a cultured human pancreatic carcinoma cell line, MIA PaCa-2. K-ras Rz (25) significantly reduced the cellular K-ras mRNA level when introduced into the MIA PaCa-2 cells. The ribozyme suppressed cell growth. K-ras Rz (25) appears capable of reversing the malignant phenotype in human pancreatic carcinoma cells.
Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Toshiyuki
T
Sakuma
Hiroshi
H
Kijima
Masatake
M
Nishi
Yoshiyuki
Y
Abe
Hitoshi
H
Yamazaki
Tetsuya
T
Mine
Masato
M
Nakamura
Yoshito
Y
Ueyama
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D016337:RNA, Catalytic; D012333:RNA, Messenger; C427204:hammerhead ribozyme