1. Genetic analysis of chemoresistance in primary murine lymphomas.
- Author
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Schmitt CA, Rosenthal CT, and Lowe SW
- 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
- 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.
- Published
- 2000
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