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

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

PMID: 22401348 [PubMed - as supplied by publisher]