Suppression of the neoplastic phenotype in vivo by an anti-ras ribozyme.
In this study, the efficacy of an anti-ras ribozyme in reversing the neoplastic phenotype was investigated. Murine NIH3T3 cells were transfected with cellular DNA from the FEMX-I human melanoma cell line expressing the activated H-ras gene. The transformed cells displayed the neoplastic phenotype in vitro and were tumorigenic in nude mice in vivo. When the transformants were transfected by a ribozyme designed to cleave only activated H-ras RNA, the transformed phenotype was abrogated. In contrast, expression of a mutant ribozyme, essentially acting only as antisense, into the transformed cells resulted in less dramatic changes in cell growth and tumorigenicity. These results reinforce the potential role of anti-oncogene ribozymes as suppressors of neoplastic growth, with possible implications for gene therapy.
Kashani-Sabet
M
M
Department of Medical Oncology, City of Hope National Medical Center, Duarte, California 91010.
Funato
T
T
Florenes
V A
VA
Fodstad
O
O
Scanlon
K J
KJ
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D011905:Genes, ras; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000517:prevention & control; D010641:Phenotype; D016337:RNA, Catalytic / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016337:RNA, Catalytic