Impact of cellular folate status and epidermal growth factor receptor expression on BCRP/ABCG2-mediated resistance to gefitinib and erlotinib View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-04

AUTHORS

C Lemos, I Kathmann, E Giovannetti, C Calhau, G Jansen, G J Peters

ABSTRACT

The effect of folate status on breast cancer resistance protein (BCRP)-mediated drug resistance to epidermal growth factor receptor (EGFR)-targeted drugs, such as gefitinib and erlotinib, was investigated in two human colon cancer cell lines, WiDr and Caco-2, of which the latter displayed greater sensitivity to these drugs due to high EGFR expression. Caco-2 LF/LV cells, growing under low-folate (LF) conditions, showed increased BCRP protein expression compared with the high-folate (HF) counterpart, which was associated with 1.8-fold resistance to gefitinib. Of note, the BCRP-specific inhibitor Ko143 completely reverted this phenotype. WiDr LF cells also showed slightly increased BCRP expression compared with the HF cells, but no differences in gefitinib sensitivity were observed. Both Caco-2 LF/LV and WiDr LF cells showed 2.4- and 2.3-fold resistance to erlotinib, respectively, compared with their HF counterparts, which mechanistically seemed BCRP unrelated, as Ko143 had no effect on erlotinib activity. In conclusion, our data suggest that in EGFR-expressing Caco-2 cells, BCRP is one of the determinants of gefitinib resistance but not of erlotinib resistance. Beyond this, folate depletion can provoke an additional decrease in gefitinib and erlotinib activity by mechanisms dependent or independent of BCRP modulation. More... »

PAGES

1120

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6604980

DOI

http://dx.doi.org/10.1038/sj.bjc.6604980

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025022176

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19277036


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