Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metastatic capability of cells at the initial stages of selection for "typical" (P-glycoprotein-mediated) multidrug resistance (MDR) was studied. Two independent sublines, 2SC/4-1 and 2SC/4-2 (11-12.4-fold resistant), and their 23- to 23.7-fold resistant 2SC/20-1 and 2SC/20-2 variants were isolated from highly tumorigenic (TrD50 = 10 cells) and highly metastatic Rous sarcoma, virus-transformed Syrian hamster fibroblast HET-SR-2SC-LNM line for resistance to colchicine. 2SC/4 cells were less tumorigenic (TrD50 = 70 cells) but as highly metastatic as parental counterparts. In contrast, both 2SC/20 variants showed a decrease in tumorigenicity (TrD50 = 320 cells) and in the capability to produce spontaneous distant metastases. 2SC/20 cells almost lost the ability to colonize lungs in experimental metastasis assay. The autophosphorylation of pp60src tyrosine kinase in 2SC/20 cells was unaltered. The results suggest that i) selection of tumor cells for low levels of "typical" MDR leads to a decrease in the frequency of spontaneous and experimental metastases, and ii) alterations of malignancy in these cells are not caused by an impairment of function of a transforming oncogene.
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PMID:Frequency of metastasis in Syrian hamster tumor cells selected for low levels of "typical" multidrug resistance. 752 75

Two independent colchicine (CLC)-resistant sublines of Rous sarcoma virus-transformed Syrian hamster fibroblasts were isolated. Each subline represented variants with 11- and 12.4-fold resistance, respectively, their 23- and 23.7-fold resistant descendants, as well as variants cultured in CLC-free medium for 10 months without loss of resistance. All variants demonstrated 'typical' multidrug resistance. The parental cells contained actin in dispersed form, as determined by rhodamine-phalloidin staining. In contrast, already in 11- and 12.4-fold resistant sublines up to 30% of cells demonstrated restored stress fibers. Cultivation in CLC-free medium leads to the accumulation of cells with a partially restored actin cytoskeleton. Putative mechanisms of up-regulation of stress fiber assembly in cells with P-glycoprotein-mediated multidrug resistance are discussed.
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PMID:Partial restoration of the actin cytoskeleton in transformed Syrian hamster fibroblasts selected for low levels of 'typical' multidrug resistance. 790 95