Stable suppression of tumorigenicity by virus-mediated RNA interference.
Most human tumors harbor multiple genetic alterations, including dominant mutant oncogenes. It is often not clear which of these oncogenes are continuously required and which, when inactivated, may inhibit tumorigenesis. Recently, we developed a vector that mediates suppression of gene expression through RNA interference. Here, we use a retroviral version of this vector to specifically and stably inhibit expression of only the oncogenic K-RAS(V12) allele in human tumor cells. Loss of expression of K-RAS(V12) leads to loss of anchorage-independent growth and tumorigenicity. These results indicate that viral delivery of small interfering RNAs can be used for tumor-specific gene therapy to reverse the oncogenic phenotype of cancer cells.
Brummelkamp
Thijn R
TR
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Bernards
René
R
Agami
Reuven
R
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000235:genetics; D005455:Fluorescent Antibody Technique; D011905:Genes, ras / Q000235:genetics* / Q000502:physiology; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics; D034622:RNA Interference / Q000502:physiology*; D012190:Retroviridae; D014162:Transfection; D014407:Tumor Cells, Cultured