bcrp - publications

Predict more bcrp - ligand interactions now!


1. Xenobiotica. 2012 Mar 8. [Epub ahead of print]

Breast cancer resistance protein (BCRP/ABCG2) localises to the nucleus in
glioblastoma multiforme cells.

Bhatia P, Bernier M, Sanghvi M, Moaddel R, Schwarting R, Ramamoorthy A, Wainer
IW.

Laboratory of Clinical Investigation, National Institute on Aging (NIA/NIH) ,
Baltimore, MD , USA.

The breast cancer resistance protein (BCRP), an ATP binding cassette (ABC) efflux
transporter, plays a role in multiple drug resistance (MDR). Previous studies of
the subcellular location of the ABC transporter P-glycoprotein indicated that
this protein is expressed in nuclear membranes. This study examines the nuclear
distribution of BCRP in seven human-derived glioblastoma (GBM) and astrocytoma
cell lines. BCRP expression was observed in the nuclear extracts of 6/7 cell
lines. Using the GBM LN229 cell line as a model, nuclear BCRP protein was
detected by immunoblotting and confocal laser microscopy. Importantly, nuclear
BCRP staining was found in a subpopulation of tumour cells in a human brain GBM
biopsy. Mitoxantrone cytotoxicity in the LN229 cell line was determined with and
without the BCRP inhibitor fumitremorgin C (FTC) and after downregulation of BCRP
with small interfering RNA (siRNA). FTC inhibition of BCRP increased mitoxantrone
cytotoxicity with a ~7-fold reduction in the IC(50) and this effect was further
potentiated in the siRNA -treated cells. In conclusion, BCRP is expressed in the
nuclear extracts of select GBM and astrocytoma cell lines and in a human GBM
tumour biopsy. Its presence in the nucleus of cancer cells suggests new role for
BCRP in MDR.

PMID: 22401348 [PubMed - as supplied by publisher]