Converting Cancer Genes into Killer Genes

Over the past decade, it has become clear that tumorigenesis is driven by alterations in genes that control cell growth or cell death. Theoretically, the proteins encoded by these genes provide excellent targets for new therapeutic agents. Here, we describe a gene therapy approach to specifically ki...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (9), p.4192-4196
Main Authors: Da Costa, Luis T., Jen, Jin, He, Tong-Chuan, Chan, Timothy A., Kinzler, Kenneth W., Vogelstein, Bert
Format: Article
Language:English
Subjects:
beta-Galactosidase - biosynthesis
Cancer
Cell Line
Cell lines
Cell Survival
Gene therapy
Genes
Genes, Bacterial
Genes, p53
Genetic Therapy
HEK293 cells
Humans
Kidney
Killing
Medical research
Medical treatment
Models, Biological
Mutagenesis, Site-Directed
Neoplasms - genetics
Neoplasms - therapy
Oncogenes
Plasmids
Point Mutation
Purine-Nucleoside Phosphorylase - biosynthesis
Recombinant Proteins - biosynthesis
Transfection
Tumor Suppressor Protein p53 - biosynthesis
Tumors
Weapons
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Summary:Over the past decade, it has become clear that tumorigenesis is driven by alterations in genes that control cell growth or cell death. Theoretically, the proteins encoded by these genes provide excellent targets for new therapeutic agents. Here, we describe a gene therapy approach to specifically kill tumor cells expressing such oncoproteins. In outline, the target oncoprotein binds to exogenously introduced gene products, resulting in transcriptional activation of a toxic gene. As an example, we show that this approach can be used to specifically kill cells overexpressing a mutant p53 gene in cell culture. The strategy may be generally applicable to neoplastic diseases in which the underlying patterns of genetic alterations or abnormal gene expression are known.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.9.4192