First Author | Schmitt CA | Year | 2000 |
Journal | Nat Med | Volume | 6 |
Issue | 9 | Pages | 1029-35 |
PubMed ID | 10973324 | Mgi Jnum | J:64496 |
Mgi Id | MGI:1889417 | Doi | 10.1038/79542 |
Citation | Schmitt CA, et al. (2000) Genetic analysis of chemoresistance in primary murine lymphomas. Nat Med 6(9):1029-35 |
abstractText | 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. |