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Transduction effect of antisense K-ras on malignant phenotypes in gastric cancer cells

 Jae J Song  ;  Heuiran Lee  ;  Eunhee Kim  ;  Yeon S Kim  ;  Nae C Yoo  ;  Jae K Roh  ;  Byung S Kim  ;  Joohang Kim 
 Cancer Letters, Vol.157(1) : 1-7, 2000 
Journal Title
 Cancer Letters 
Issue Date
Animals ; Cell Division/physiology ; Down-Regulation ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Genes, ras/genetics* ; Genetic Therapy ; Genetic Vectors ; Humans ; Male ; Mice ; Mice, Nude ; Mutation/genetics ; Neoplasm Transplantation ; Oligoribonucleotides, Antisense/genetics* ; Oncogene Protein p21(ras)/biosynthesis ; Oncogene Protein p21(ras)/genetics ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Retroviridae/genetics ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/pathology ; Transduction, Genetic* ; Tumor Cells, Cultured
Gastric cancer ; K-ras ; Antisense ; Gene therapy
The antitumoral effects of antisense RNA to K-ras were investigated in gastric cancer cell lines by examining the level of K-ras expression and the tumorigenicity in vitro and in vivo. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), DNA sequencing, and immunoblotting analysis revealed that YCC-1 gastric cancer cells overexpressed wild type K-ras, whereas YCC-2 cells had a homozygous mutation in codon 12 from GGT (glycine) to AGT (serine), while SNU-1 cells had a heterozygous mutation to GAT (asparagine) in the identical position. Both YCC-1 and YCC-2 cells were transduced by LNC-AS/K-ras containing the antisense 2.2 kb genomic K-ras DNA fragment covering exon 2 and exon 3 specific for K-ras. The application of antisense K-ras significantly downregulated the expression of K-ras and had no influence on the expression of either H-ras or N-ras. The antisense-transduced YCC-2 cells grew considerably slower than the control group transduced by LNCX, whereas the growth inhibition of antisense-transduced YCC-1 cells was less prominent than that of transduced YCC-2 cells. In addition, the tumorigenicity of YCC-2 cells transduced by LNC-AS/K-ras was totally lost. Therefore, our results imply that the specific inhibition of K-ras p21 protein can be accomplished by introducing the antisense covering the K-ras- specific region to gastric cancer cells with aberrant K-ras expression, resulting in a reduction of the growth rate and suppression of tumorigenicity.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Roh, Jae Kyung(노재경)
Song, Jae Jin(송재진) ORCID logo https://orcid.org/0000-0001-8183-9550
Yoo, Nae Choon(유내춘)
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