Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/90965
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Type: Journal article
Title: Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer
Author: Gao, B.
Russell, A.
Beesley, J.
Chen, X.
Healey, S.
Henderson, M.
Wong, M.
Emmanuel, C.
Galletta, L.
Johnatty, S.
Bowtell, D.
Australian Ovarian Cancer Study Group
Haber, M.
Norris, M.
Harnett, P.
Chenevix-Trench, G.
Balleine, R.
Defazio, A.
Citation: Scientific Reports, 2014; 4(1):4669-1-4669-9
Publisher: Nature Publishing Groups
Issue Date: 2014
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Bo Gao, Amanda Russell, Jonathan Beesley, Xiao Qing Chen, Sue Healey, Michelle Henderson, Mark Wong, Catherine Emmanuel, Laura Galletta, Sharon E. Johnatty, David Bowtell, Australian Ovarian Cancer Study Group, Michelle Haber, Murray Norris, Paul Harnett, Georgia Chenevix-Trench, Rosemary L. Balleine, Anna deFazio
Abstract: ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may underlie the association. Using cell-based models, we evaluated the correlations between ABCB1 expression, polymorphisms, transporter activity and paclitaxel sensitivity in ovarian cancer (n = 10) and lymphoblastoid (n = 19) cell lines. Close associations between ABCB1 expression, transporter function and paclitaxel sensitivity were found in lymphoblastoid cell lines, although we could not demonstrate an association with common SNPs. In ovarian cancer cell lines, ABCB1 expression was low and the association between expression and function was lost. These results suggest that ABCB1 related survival difference in ovarian cancer patients is more likely to be due to differential whole body paclitaxel clearance mediated by normal cells rather than a direct effect on cancer cells.
Keywords: Ovarian cancer; Translational research
Description: Martin Oehler is a member of the Australian Ovarian Cancer Study Group
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the image. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
RMID: 0030014924
DOI: 10.1038/srep04669
Grant ID: http://purl.org/au-research/grants/nhmrc/400413
http://purl.org/au-research/grants/nhmrc/400281
Appears in Collections:Paediatrics publications

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