Reichle, A and Diddens, H and Altmayr, F and Rastetter, J and Andreesen, R (1995) Beta-tubulin and P-glycoprotein: Major determinants of vincristine accumulation in B-CLL cells. LEUKEMIA RESEARCH, 19 (11). pp. 823-829. ISSN 0145-2126,
Full text not available from this repository.Abstract
Vincristine (VCR) accumulation in chronic lymphatic leukemia of B-cell origin (B-CLL) has recently been shown not to be inversely correlated to P-glycoprotein (PGP) levels. Therefore, we studied, in addition to PGP expression and accumulation of VCR, the cellular beta-tubulin content in quiescent and rhlL-2 activated B-CLL cells. VCR mediates cytotoxicity by binding to tubulin. Constitutive P-tubulin levels in B-CLL cells varied considerably. Upon activation with rhlL-2, beta-tubulin expression increased significantly. Therefore, tubulin levels could be correlated over a wide range to VCR accumulation. When the PGP-mediated drug efflux was blocked by verapamil (VRP), tubulin levels correlated linearly to VCR accumulation. All B-CLL cases expressed PGP at different levels. There was no linear correlation between PGP expression and VCR accumulation. A modulation factor m was defined as a quotient of VCR accumulation in the presence and absence of VRP to define the extent by which VRP inhibited a steady-state accumulation of VCR. The factor allowed discrimination between B-CLLs expressing low versus high PGP, irrespective of the levels of tubulin. However, PGP and beta-tubulin levels together were predictive for VCR accumulation in steady state. There was no uniform accumulation defect for VCR in B-cell CLL because beta-tubulin and PGP were expressed independently. Non PGP-mediated VCR transport seems to play a minor role in B-cell CLL. Leukemia-associated varying of cytoskeletal organization in B-cell CLL might be one reason for the diverse cellular responses to receptor-mediated signals.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC LYMPHOCYTIC-LEUKEMIA; RESISTANCE; EXPRESSION; CYTOSKELETON; ORGANIZATION; MICROTUBULE; GENE; MECHANISMS; AGENTS; multidrug resistance; tubulin; vincristine; B-CLL |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/52238 |
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