We examined the role of @entity11092 ( @entity11092 ) in the emergence of @entity2664 (MX) cross-resistance in a MCF7 @entity0 cell line selected for resistance to @entity2879 . The resistant cell line, MCF7/VP, expresses high levels of @entity11092 , whereas the parental cell line, MCF7/WT, does not. MCF7/VP cells are 6-10-fold cross-resistant to MX when compared with MCF7/WT cells. Drug transport studies in intact MCF7/VP cells revealed that MX resistance is associated with @entity146 due to enhanced MX efflux. MX efflux is @entity855 dependent and inhibited by @entity17732 and @entity205 . Inhibition of MX efflux with these agents sensitizes cells to MX @entity137 and partially reverses MX resistance in MCF7/VP cells. Whereas resistance is partially attributable to increased MX efflux in @entity11092 -expressing MCF7/VP cells, we found no evidence for @entity2041 or other conjugates of MX in these cells. Moreover, @entity2041 depletion with @entity3016 had no effect on MX transport or sensitivity in MCF7/VP cells. @entity11092 substrates are generally amphiphilic anions such as @entity2041 conjugates or require the presence of physiological levels of @entity2041 for @entity11092 -mediated transport. Therefore we conclude that @entity11092 overexpression is unlikely to be responsible for increased MX efflux and resistance in MCF7/VP cells. In considering the potential involvement of other MRP family isoforms, a 3-fold increase in the expression of @entity22477 was observed in MCF7/VP cells. However, stable expression of a transduced @entity22477 expression vector in MCF7/WT cells failed to confer MX resistance. Because other transporters known to be associated with MX resistance, including P-glycoprotein and @entity10430 / @entity10430 ( @entity10430 ), are not expressed in MCF7/VP cells, we conclude that increased MX efflux and resistance in MCF7/VP cells is attributable to a novel transport mechanism or that MX represents a novel class of cationic, @entity2041 -independent @entity11092 substrates.

Resistance to @entity2664 in multidrug-resistant MCF7 XXXX cells: evaluation of @entity2664 transport and the role of multidrug resistance protein family proteins.

@entity17732 :: ('MESH:D013442', 'Chemical') :: ['sulfinpyrazone'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity146 :: ('MESH:D001523', 'Disease') :: ['reduced MX accumulation'] @entity10430 :: ('9429', 'Gene') :: ['MXR', 'ABCG2', 'BCRP'] @entity2664 :: ('MESH:D008942', 'Chemical') :: ['mitoxantrone'] @entity2041 :: ('MESH:D005978', 'Chemical') :: ['glutathione'] @entity22477 :: ('10057', 'Gene') :: ['MRP5'] @entity2879 :: ('MESH:D005047', 'Chemical') :: ['etoposide'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporin A'] @entity11092 :: ('4363', 'Gene') :: ['multidrug resistance protein (MRP) 1', 'MRP1', 'ABCC1'] @entity3016 :: ('MESH:D019328', 'Chemical') :: ['buthionine sulfoximine'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer']
