title: Hammerhead ribozyme specifically inhibits mutant K-ras mRNA of human pancreatic cancer cells.
abstract: We have evaluated the efficacy of an anti-K-ras hammerhead ribozyme targeted against GUU-mutated codon 12 of the K-ras gene in a cell-free system as well as in cultured pancreatic carcinoma cell lines. In the cell-free system, the anti-K-ras ribozyme specifically cleaved K-ras RNA with GUU-mutation at codon 12, but not other triplet sequences at codon 12 of K-ras RNA. In the cell culture system, the anti-K-ras ribozyme significantly reduced K-ras mRNA level (GUU-mutated codon 12) in Capan-1 pancreatic carcinoma cells, but less significantly suppressed K-ras mRNA in Capan-2 (GUU/GGU heterozygous-mutation at codon 12) or MIA PaCa-2 (UGU-mutated codon 12) pancreatic carcinoma cells. The ribozyme inhibited proliferation of transfected Capan-1 cells. These results suggest that this ribozyme selectively recognizes single-base mutation of K-ras mRNA and is able to reverse the malignant phenotype in human pancreatic carcinoma cells.
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsuchida
authors.forename: H
authors.initials: H
authors.lastname: Kijima
authors.forename: Y
authors.initials: Y
authors.lastname: Oshika
authors.forename: T
authors.initials: T
authors.lastname: Tokunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Yamazaki
authors.forename: N
authors.initials: N
authors.lastname: Tamaoki
authors.forename: Y
authors.initials: Y
authors.lastname: Ueyama
authors.forename: K J
authors.initials: KJ
authors.lastname: Scanlon
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002474:Cell-Free System; D015536:Down-Regulation / Q000235:genetics; D011905:Genes, ras; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D016297:Mutagenesis, Site-Directed; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016337:RNA, Catalytic / Q000502:physiology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D006131:Growth Inhibitors; D016337:RNA, Catalytic; D012333:RNA, Messenger