Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA.
A human lung cancer cell line (H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a 2-kilobase genomic segment of the K-ras protooncogene in antisense orientation. Translation of the mutated K-ras mRNA in H460a cells was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A 3-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA. However, cells remained viable despite the absence of K-ras expression. The growth of H460a tumors in nu/nu mice was substantially reduced by expressed K-ras antisense RNA.
Mukhopadhyay
T
T
Department of Thoracic Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Tainsky
M
M
Cavender
A C
AC
Roth
J A
JA
D000818:Animals; D011905:Genes, ras; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis; D016372:RNA, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D016372:RNA, Antisense; D012333:RNA, Messenger; D016283:Proto-Oncogene Proteins p21(ras)