Please use this identifier to cite or link to this item: http://hdl.handle.net/11054/803
Title: Paclitaxel sensitivity in relation to ABCD1 expression, efflux and single nucleotide polymorphisms in ovarian cancer.
Authors: Gao, Bo
Russell, Amanda
Beesley, Jonathon
Chen, Xiao Quing
Healey, Sue
Henderson, Michelle
Wong, Mark
Emmanuel, Catherine
Galleta, Laura
Johnatty, Sharon E.
Bowtell, David
Haber, Michelle
Norris, Murray
Harnett, Paul
Chenevix-Trench, Georgia
Balleine, Rosemary L.
deFazio, Anna
Issue Date: 2014
Publisher: Nature Publishing Group
Place of publication: London, UK
Journal title: Scientific Reports
Volume: 4
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.
URI: http://hdl.handle.net/11054/803
metadata.dc.relation.uri: http://www.nature.com/search?author=galletta&date_range=2014-2015&journal=srep&order=relevance&q=ovarian%20cancer%20is%20the%20seventh%20leading%20cause%20of%20cancer%20mortality%20among%20women%20globally&title=paclitaxel%20sensitivity&volume=4
ISSN: 2045 2322 (online)
Internal ID Number: 00801
Health Subject: ADENOSINE TRIPHOSPHATE
ANTEOPLASTIC AGENTS
CELL LINE
OVARIAN NEOPLASMS
PALITAXEL
POLYMORPHISM, GENETIC
PLOYMORPHISM, SINGLE NUCLEOTIDE
Type: Journal Article
Article
Appears in Collections:Research Output

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