Breast cancer resistance protein is a MTX and MTX-polyglutamate transporter.

2004 FEB 5 - (NewsRx.com & NewsRx.net) -- Study data show that that breast cancer resistance protein (BCRP) is a methotrexate (MTX) and MTX-polyglutamate transporter and reveal a possible mechanism by which it confers resistance.

According to recent research published in the journal Cancer Research, "The existence of an ATP-dependent MTX efflux mechanism has long been postulated; however, until recently, the molecular components were largely unknown. We have previously demonstrated a role for the ATP-binding cassette transporter BCRP in MTX resistance (Volk et al., Cancer Res., 2002; 62:5035-5040."

"Resistance to this antifolate directly correlated with BCRP expression, and was reversible by the BCRP inhibitors fumitremorgin C and GF120918. Here, we provide evidence for BCRP as a MTX-transporter using an in vitro membrane vesicle system," wrote E.L. Volk and colleagues, New York State Department of Health, Wadsworth Center.

"Inside-out membrane vesicles were generated from both drug-selected and stably transfected cell lines expressing either wild-type (Arg482) or mutant (Gly482) variants of BCRP. In the presence of the wild-type variant of BCRP, transport of MTX into vesicles was ATP-dependent, osmotically sensitive, and inhibited by fumitremorgin C," the researchers wrote.

"In contrast, no transport was observed in vesicles containing the mutant form of BCRP. Wild-type BCRP appeared to have low affinity, but high capacity, for the transport of MTX, with ...