Gene Therapy of Rat 9L Gliosarcoma Tumors by Transduction with Selectable Genes Does Not Require Drug Selection

9L rat glioma cells have been used as a model for brain tumor therapies. It has been reported that in vivo infection of 9L cells with a replication-defective retrovirus expressing the herpes simplex thymidine kinase gene resulted in decreased tumor formation following treatment with the antiviral dr...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-08, Vol.91 (17), p.8185-8189
Main Authors: Tapscott, S. J., Miller, A. D., Olson, J. M., Berger, M. S., Groudine, M., Spence, A. M.
Format: Article
Language:English
Subjects:
Animals
Cell Division
Cell growth
Cell lines
Cells
Cellular immunity
Cytomegalovirus - genetics
Ganciclovir - toxicity
Genes
Genetic Therapy
Genetic Vectors
Glioma
Gliosarcoma - pathology
Gliosarcoma - therapy
Humans
Kanamycin Kinase
Kinetics
Male
Medical research
Moloney murine leukemia virus - genetics
Phosphotransferases (Alcohol Group Acceptor) - biosynthesis
Phosphotransferases (Alcohol Group Acceptor) - genetics
Plasmids
Rats
Rats, Inbred F344
Recombinant Fusion Proteins - biosynthesis
Retroviral vectors
Rodents
Simplexvirus - genetics
T lymphocytes
Thymidine Kinase - biosynthesis
Thymidine Kinase - genetics
Transduction, Genetic
Transfection
Tumor cell line
Tumor Cells, Cultured
Tumors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:9L rat glioma cells have been used as a model for brain tumor therapies. It has been reported that in vivo infection of 9L cells with a replication-defective retrovirus expressing the herpes simplex thymidine kinase gene resulted in decreased tumor formation following treatment with the antiviral drug ganciclovir. In the study reported here, rats were injected either intracerebrally or subcutaneously with 9L glioma cells expressing a chimeric hygromycin phosphotransferase-thymidine kinase fusion protein or with unmodified 9L cells. Tumor formation was decreased in the rats receiving modified cells, even in the absence of treatment with ganciclovir. Suppression of tumor growth was also observed with cells modified to express the intracellular selectable marker neomycin phosphotransferase. These results indicate that an intracellular selectable marker, in the absence of pharmacologic selection, can inhibit tumor growth of 9L cells. The demonstration that intracellular marker genes can negatively influence the survival of transplanted cells has important implications for in vivo studies that use genetically modified cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.17.8185