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Genetic analysis of chemoresistance in primary murine lymphomas.
- Source :
-
Nature medicine [Nat Med] 2000 Sep; Vol. 6 (9), pp. 1029-35. - Publication Year :
- 2000
-
Abstract
- Understanding the basis of chemoresistance is a principal goal of molecular oncology. We have exploited a murine lymphoma model and retroviral gene transfer to rapidly generate a series of spontaneous tumors differing only in a gene of interest, and subsequently studied the impact of the test gene on the treatment sensitivity of tumors at their natural site. We demonstrate that the Bcl-2 oncoprotein produces multi-drug resistance when assessed in primary lymphomas in vivo. In contrast, this effect was dramatically reduced when the primary lymphomas were subjected to long-term culture, and completely missed in the standard clonogenic survival assay. This model highlights the importance of physiological test systems to address the complexity of clinical drug resistance and provides a novel strategy to evaluate compounds targeting specific genetic lesions.
- Subjects :
- Adaptation, Biological
Animals
Clone Cells
Culture Techniques methods
Gene Transfer Techniques
Mice
Mice, Transgenic
Neoplasms, Experimental
Proto-Oncogene Proteins c-myc biosynthesis
Proto-Oncogene Proteins c-myc genetics
Retroviridae genetics
Tumor Cells, Cultured
Drug Resistance, Multiple genetics
Genes, bcl-2
Lymphoma genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1078-8956
- Volume :
- 6
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 10973324
- Full Text :
- https://doi.org/10.1038/79542