Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

Bo Gao; Amanda Russell; Jonathan Beesley; Xiao Qing Chen; Sue Healey; Michelle Henderson; Mark Wong; Catherine Emmanuel; Laura Galletta; Sharon E. Johnatty; David Bowtell; Michelle Haber; Murray Norris; Paul Harnett; Georgia Chenevix-Trench; Rosemary L. Balleine; Anna Defazio; Dorota Gertig; Adèle Green; Penelope Webb; Jillian Hung; Sue Moore; Nadia Traficante; Sian Fereday; Karen Harrap; Troy Sadkowsky; Nirmala Pandeya; Robin Stuart-Harris; Fred Kirsten; Josie Rutovitz; Peter Clingan; Amanda Glasgow; Anthony Proietto; Stephen Braye; Greg Otton; Jennifer Shannon; Tony Bonaventura; James Stewart; Stephen Begbie; Michael Friedlander; David Bell; Sally Baron-Hay; Alan Ferrier; Greg Gard; David Nevell; Nick Pavlakis; Sue Valmadre; Barbara Young; Catherine Camaris; Roger Crouch; Lyndal Edwards; Neville Hacker; Donald Marsden; Greg Robertson; Phillip Beale; Jane Beith; Jonothan Carter; Chris Dalrymple; Anne Hamilton; Roger Houghton; Peter Russell; Matthew Links; John Grygiel; Jane Hill; Alison Brand; Karen Byth; Richard Jaworski; Raghwa Sharma; Anita Achen; Gerard Wain; Bruce Ward; David Papadimos; Alex Crandon; Margaret Cummings; Ken Horwood; Andreas Obermair; Lew Perrin; David Wyld; Jim Nicklin; Margaret Davy; Martin K. Oehler; Chris Hall; Tom Dodd; Tabitha Healy; Ken Pittman; Doug Henderson; John Miller; John Pierdes; Penny Blomfield; David Challis; Robert McIntosh; Andrew Parker; Bob Brown; Robert Rome; David Allen; Peter Grant; Simon Hyde; Rohan Laurie; Melissa Robbie; David Healy; Tom Jobling; Tom Manolitsas; Jane McNealage; Peter Rogers; Beatrice Susil; Eric Sumithran; Ian Simpson; Kelly Phillips; Danny Rischin; Stephen Fox; Daryl Johnson; Paul Waring; Stephen Lade; Maurice Loughrey; Neil O'Callaghan; William Murray; Virginia Billson; Jan Pyman; Debra Neesham; Michael Quinn; Craig Underhill; Richard Bell; Leong Fook Ng; Robert Blum; Vinod Ganju; Ian Hammond; Yee Leung; Anthony McCartney; Martin Buck; Izak Haviv; David Purdie; David Whiteman; Nikolajs Zeps; Mary Rose Malt; Anne Mellon; Randall Robertson; Trish Vanden Bergh; Marian Jones; Patricia Mackenzie; Jane Maidens; Kath Nattress; Yoke Eng Chiew; Annie Stenlake; Helen Sullivan; Barbara Alexander; Pat Ashover; Sue Brown; Tracy Corrish; Lyn Green; Leah Jackman; Kaltin Ferguson; Karen Martin; Adam Martyn; Barbara Ranieri; Jo White; Victoria Jayde; Leanne Bowes; Pamela Mamers; Debra Giles; Joy Hendley; Katherine Alsop; Trudy Schmidt; Helen Shirley; Colleen Ball; Cherry Young; Suzanna Viduka; Hoa Tran; Sanela Bilic; Lydia Glavinas; Julia Brooks

doi:10.1038/srep04669

Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

Bo Gao, Amanda Russell, Jonathan Beesley, Xiao Qing Chen, Sue Healey, Michelle Henderson, Mark Wong, Catherine Emmanuel, Laura Galletta, Sharon E. Johnatty, David Bowtell, Michelle Haber, Murray Norris, Paul Harnett, Georgia Chenevix-Trench, Rosemary L. Balleine, Anna Defazio, Dorota Gertig, Adèle Green, Penelope WebbJillian Hung, Sue Moore, Nadia Traficante, Sian Fereday, Karen Harrap, Troy Sadkowsky, Nirmala Pandeya, Robin Stuart-Harris, Fred Kirsten, Josie Rutovitz, Peter Clingan, Amanda Glasgow, Anthony Proietto, Stephen Braye, Greg Otton, Jennifer Shannon, Tony Bonaventura, James Stewart, Stephen Begbie, Michael Friedlander, David Bell, Sally Baron-Hay, Alan Ferrier, Greg Gard, David Nevell, Nick Pavlakis, Sue Valmadre, Barbara Young, Catherine Camaris, Roger Crouch, Lyndal Edwards, Neville Hacker, Donald Marsden, Greg Robertson, Phillip Beale, Jane Beith, Jonothan Carter, Chris Dalrymple, Anne Hamilton, Roger Houghton, Peter Russell, Matthew Links, John Grygiel, Jane Hill, Alison Brand, Karen Byth, Richard Jaworski, Raghwa Sharma, Anita Achen, Gerard Wain, Bruce Ward, David Papadimos, Alex Crandon, Margaret Cummings, Ken Horwood, Andreas Obermair, Lew Perrin, David Wyld, Jim Nicklin, Margaret Davy, Martin K. Oehler, Chris Hall, Tom Dodd, Tabitha Healy, Ken Pittman, Doug Henderson, John Miller, John Pierdes, Penny Blomfield, David Challis, Robert McIntosh, Andrew Parker, Bob Brown, Robert Rome, David Allen, Peter Grant, Simon Hyde, Rohan Laurie, Melissa Robbie, David Healy, Tom Jobling, Tom Manolitsas, Jane McNealage, Peter Rogers, Beatrice Susil, Eric Sumithran, Ian Simpson, Kelly Phillips, Danny Rischin, Stephen Fox, Daryl Johnson, Paul Waring, Stephen Lade, Maurice Loughrey, Neil O'Callaghan, William Murray, Virginia Billson, Jan Pyman, Debra Neesham, Michael Quinn, Craig Underhill, Richard Bell, Leong Fook Ng, Robert Blum, Vinod Ganju, Ian Hammond, Yee Leung, Anthony McCartney, Martin Buck, Izak Haviv, David Purdie, David Whiteman, Nikolajs Zeps, Mary Rose Malt, Anne Mellon, Randall Robertson, Trish Vanden Bergh, Marian Jones, Patricia Mackenzie, Jane Maidens, Kath Nattress, Yoke Eng Chiew, Annie Stenlake, Helen Sullivan, Barbara Alexander, Pat Ashover, Sue Brown, Tracy Corrish, Lyn Green, Leah Jackman, Kaltin Ferguson, Karen Martin, Adam Martyn, Barbara Ranieri, Jo White, Victoria Jayde, Leanne Bowes, Pamela Mamers, Debra Giles, Joy Hendley, Katherine Alsop, Trudy Schmidt, Helen Shirley, Colleen Ball, Cherry Young, Suzanna Viduka, Hoa Tran, Sanela Bilic, Lydia Glavinas, Julia Brooks

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English
Article number	4669
Journal	Scientific Reports
Volume	4
DOIs	https://doi.org/10.1038/srep04669
State	Published - 9 May 2014
Externally published	Yes

Bibliographical note

Funding Information:
This project was supported by the National Health and Medical Research Council (NHMRC) of Australia (scholarship to B.G.), Cancer Institute New South Wales and Cancer Australia (552481). AdeF is funded by the University of Sydney Cancer Research Fund and the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre. We gratefully acknowledge the cooperation of the institutions that supported the study. We also acknowledge the contribution of Australian Ovarian Cancer Study Group (full list can be found at http://www.aocstudy.org), all study nurses and research assistants and would like to thank all of the women who participated in AOCS. AOCS was supported by U.S. Army Medical Research and Materiel Command DAMD17-01-1-0729, NHMRC Enabling Grant 400413 and Project Grant 400281, the Cancer Council Tasmania and the Cancer Foundation of Western Australia.

Funding

This project was supported by the National Health and Medical Research Council (NHMRC) of Australia (scholarship to B.G.), Cancer Institute New South Wales and Cancer Australia (552481). AdeF is funded by the University of Sydney Cancer Research Fund and the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre. We gratefully acknowledge the cooperation of the institutions that supported the study. We also acknowledge the contribution of Australian Ovarian Cancer Study Group (full list can be found at http://www.aocstudy.org), all study nurses and research assistants and would like to thank all of the women who participated in AOCS. AOCS was supported by U.S. Army Medical Research and Materiel Command DAMD17-01-1-0729, NHMRC Enabling Grant 400413 and Project Grant 400281, the Cancer Council Tasmania and the Cancer Foundation of Western Australia.

Funders	Funder number
Cancer Foundation of Western Australia
Cancer Institute New South Wales and Cancer Australia	552481
Sydney-West Translational Cancer Research Centre
Medical Research and Materiel Command	DAMD17-01-1-0729
National Health and Medical Research Council	400281, 400413
Cancer Council Tasmania
Cancer Institute NSW
University of Sydney

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/srep04669

https://www.nature.com/articles/srep04669.pdfLicense: CC BY-NC-ND

Cite this

Gao, B., Russell, A., Beesley, J., Chen, X. Q., Healey, S., Henderson, M., Wong, M., Emmanuel, C., Galletta, L., Johnatty, S. E., Bowtell, D., Haber, M., Norris, M., Harnett, P., Chenevix-Trench, G., Balleine, R. L., Defazio, A., Gertig, D., Green, A., ... Brooks, J. (2014). Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer. Scientific Reports, 4, Article 4669. https://doi.org/10.1038/srep04669

@article{2a2a73253b4848debfc24cf79bd36412,

title = "Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer",

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.",

author = "Bo Gao and Amanda Russell and Jonathan Beesley and Chen, {Xiao Qing} and Sue Healey and Michelle Henderson and Mark Wong and Catherine Emmanuel and Laura Galletta and Johnatty, {Sharon E.} and David Bowtell and Michelle Haber and Murray Norris and Paul Harnett and Georgia Chenevix-Trench and Balleine, {Rosemary L.} and Anna Defazio and Dorota Gertig and Ad{\`e}le Green and Penelope Webb and Jillian Hung and Sue Moore and Nadia Traficante and Sian Fereday and Karen Harrap and Troy Sadkowsky and Nirmala Pandeya and Robin Stuart-Harris and Fred Kirsten and Josie Rutovitz and Peter Clingan and Amanda Glasgow and Anthony Proietto and Stephen Braye and Greg Otton and Jennifer Shannon and Tony Bonaventura and James Stewart and Stephen Begbie and Michael Friedlander and David Bell and Sally Baron-Hay and Alan Ferrier and Greg Gard and David Nevell and Nick Pavlakis and Sue Valmadre and Barbara Young and Catherine Camaris and Roger Crouch and Lyndal Edwards and Neville Hacker and Donald Marsden and Greg Robertson and Phillip Beale and Jane Beith and Jonothan Carter and Chris Dalrymple and Anne Hamilton and Roger Houghton and Peter Russell and Matthew Links and John Grygiel and Jane Hill and Alison Brand and Karen Byth and Richard Jaworski and Raghwa Sharma and Anita Achen and Gerard Wain and Bruce Ward and David Papadimos and Alex Crandon and Margaret Cummings and Ken Horwood and Andreas Obermair and Lew Perrin and David Wyld and Jim Nicklin and Margaret Davy and Oehler, {Martin K.} and Chris Hall and Tom Dodd and Tabitha Healy and Ken Pittman and Doug Henderson and John Miller and John Pierdes and Penny Blomfield and David Challis and Robert McIntosh and Andrew Parker and Bob Brown and Robert Rome and David Allen and Peter Grant and Simon Hyde and Rohan Laurie and Melissa Robbie and David Healy and Tom Jobling and Tom Manolitsas and Jane McNealage and Peter Rogers and Beatrice Susil and Eric Sumithran and Ian Simpson and Kelly Phillips and Danny Rischin and Stephen Fox and Daryl Johnson and Paul Waring and Stephen Lade and Maurice Loughrey and Neil O'Callaghan and William Murray and Virginia Billson and Jan Pyman and Debra Neesham and Michael Quinn and Craig Underhill and Richard Bell and Ng, {Leong Fook} and Robert Blum and Vinod Ganju and Ian Hammond and Yee Leung and Anthony McCartney and Martin Buck and Izak Haviv and David Purdie and David Whiteman and Nikolajs Zeps and Malt, {Mary Rose} and Anne Mellon and Randall Robertson and {Vanden Bergh}, Trish and Marian Jones and Patricia Mackenzie and Jane Maidens and Kath Nattress and Chiew, {Yoke Eng} and Annie Stenlake and Helen Sullivan and Barbara Alexander and Pat Ashover and Sue Brown and Tracy Corrish and Lyn Green and Leah Jackman and Kaltin Ferguson and Karen Martin and Adam Martyn and Barbara Ranieri and Jo White and Victoria Jayde and Leanne Bowes and Pamela Mamers and Debra Giles and Joy Hendley and Katherine Alsop and Trudy Schmidt and Helen Shirley and Colleen Ball and Cherry Young and Suzanna Viduka and Hoa Tran and Sanela Bilic and Lydia Glavinas and Julia Brooks",

note = "Funding Information: This project was supported by the National Health and Medical Research Council (NHMRC) of Australia (scholarship to B.G.), Cancer Institute New South Wales and Cancer Australia (552481). AdeF is funded by the University of Sydney Cancer Research Fund and the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre. We gratefully acknowledge the cooperation of the institutions that supported the study. We also acknowledge the contribution of Australian Ovarian Cancer Study Group (full list can be found at http://www.aocstudy.org), all study nurses and research assistants and would like to thank all of the women who participated in AOCS. AOCS was supported by U.S. Army Medical Research and Materiel Command DAMD17-01-1-0729, NHMRC Enabling Grant 400413 and Project Grant 400281, the Cancer Council Tasmania and the Cancer Foundation of Western Australia.",

year = "2014",

month = may,

day = "9",

doi = "10.1038/srep04669",

language = "אנגלית",

volume = "4",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

Gao, B, Russell, A, Beesley, J, Chen, XQ, Healey, S, Henderson, M, Wong, M, Emmanuel, C, Galletta, L, Johnatty, SE, Bowtell, D, Haber, M, Norris, M, Harnett, P, Chenevix-Trench, G, Balleine, RL, Defazio, A, Gertig, D, Green, A, Webb, P, Hung, J, Moore, S, Traficante, N, Fereday, S, Harrap, K, Sadkowsky, T, Pandeya, N, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Hamilton, A, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Sharma, R, Achen, A, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, McIntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Jobling, T, Manolitsas, T, McNealage, J, Rogers, P, Susil, B, Sumithran, E, Simpson, I, Phillips, K, Rischin, D, Fox, S, Johnson, D, Waring, P, Lade, S, Loughrey, M, O'Callaghan, N, Murray, W, Billson, V, Pyman, J, Neesham, D, Quinn, M, Underhill, C, Bell, R, Ng, LF, Blum, R, Ganju, V, Hammond, I, Leung, Y, McCartney, A, Buck, M, Haviv, I, Purdie, D, Whiteman, D, Zeps, N, Malt, MR, Mellon, A, Robertson, R, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Bowes, L, Mamers, P, Giles, D, Hendley, J, Alsop, K, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L & Brooks, J 2014, 'Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer', Scientific Reports, vol. 4, 4669. https://doi.org/10.1038/srep04669

TY - JOUR

T1 - Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

AU - Gao, Bo

AU - Russell, Amanda

AU - Beesley, Jonathan

AU - Chen, Xiao Qing

AU - Healey, Sue

AU - Henderson, Michelle

AU - Wong, Mark

AU - Emmanuel, Catherine

AU - Galletta, Laura

AU - Johnatty, Sharon E.

AU - Bowtell, David

AU - Haber, Michelle

AU - Norris, Murray

AU - Harnett, Paul

AU - Chenevix-Trench, Georgia

AU - Balleine, Rosemary L.

AU - Defazio, Anna

AU - Gertig, Dorota

AU - Green, Adèle

AU - Webb, Penelope

AU - Hung, Jillian

AU - Moore, Sue

AU - Traficante, Nadia

AU - Fereday, Sian

AU - Harrap, Karen

AU - Sadkowsky, Troy

AU - Pandeya, Nirmala

AU - Stuart-Harris, Robin

AU - Kirsten, Fred

AU - Rutovitz, Josie

AU - Clingan, Peter

AU - Glasgow, Amanda

AU - Proietto, Anthony

AU - Braye, Stephen

AU - Otton, Greg

AU - Shannon, Jennifer

AU - Bonaventura, Tony

AU - Stewart, James

AU - Begbie, Stephen

AU - Friedlander, Michael

AU - Bell, David

AU - Baron-Hay, Sally

AU - Ferrier, Alan

AU - Gard, Greg

AU - Nevell, David

AU - Pavlakis, Nick

AU - Valmadre, Sue

AU - Young, Barbara

AU - Camaris, Catherine

AU - Crouch, Roger

AU - Edwards, Lyndal

AU - Hacker, Neville

AU - Marsden, Donald

AU - Robertson, Greg

AU - Beale, Phillip

AU - Beith, Jane

AU - Carter, Jonothan

AU - Dalrymple, Chris

AU - Hamilton, Anne

AU - Houghton, Roger

AU - Russell, Peter

AU - Links, Matthew

AU - Grygiel, John

AU - Hill, Jane

AU - Brand, Alison

AU - Byth, Karen

AU - Jaworski, Richard

AU - Sharma, Raghwa

AU - Achen, Anita

AU - Wain, Gerard

AU - Ward, Bruce

AU - Papadimos, David

AU - Crandon, Alex

AU - Cummings, Margaret

AU - Horwood, Ken

AU - Obermair, Andreas

AU - Perrin, Lew

AU - Wyld, David

AU - Nicklin, Jim

AU - Davy, Margaret

AU - Oehler, Martin K.

AU - Hall, Chris

AU - Dodd, Tom

AU - Healy, Tabitha

AU - Pittman, Ken

AU - Henderson, Doug

AU - Miller, John

AU - Pierdes, John

AU - Blomfield, Penny

AU - Challis, David

AU - McIntosh, Robert

AU - Parker, Andrew

AU - Brown, Bob

AU - Rome, Robert

AU - Allen, David

AU - Grant, Peter

AU - Hyde, Simon

AU - Laurie, Rohan

AU - Robbie, Melissa

AU - Healy, David

AU - Jobling, Tom

AU - Manolitsas, Tom

AU - McNealage, Jane

AU - Rogers, Peter

AU - Susil, Beatrice

AU - Sumithran, Eric

AU - Simpson, Ian

AU - Phillips, Kelly

AU - Rischin, Danny

AU - Fox, Stephen

AU - Johnson, Daryl

AU - Waring, Paul

AU - Lade, Stephen

AU - Loughrey, Maurice

AU - O'Callaghan, Neil

AU - Murray, William

AU - Billson, Virginia

AU - Pyman, Jan

AU - Neesham, Debra

AU - Quinn, Michael

AU - Underhill, Craig

AU - Bell, Richard

AU - Ng, Leong Fook

AU - Blum, Robert

AU - Ganju, Vinod

AU - Hammond, Ian

AU - Leung, Yee

AU - McCartney, Anthony

AU - Buck, Martin

AU - Haviv, Izak

AU - Purdie, David

AU - Whiteman, David

AU - Zeps, Nikolajs

AU - Malt, Mary Rose

AU - Mellon, Anne

AU - Robertson, Randall

AU - Vanden Bergh, Trish

AU - Jones, Marian

AU - Mackenzie, Patricia

AU - Maidens, Jane

AU - Nattress, Kath

AU - Chiew, Yoke Eng

AU - Stenlake, Annie

AU - Sullivan, Helen

AU - Alexander, Barbara

AU - Ashover, Pat

AU - Brown, Sue

AU - Corrish, Tracy

AU - Green, Lyn

AU - Jackman, Leah

AU - Ferguson, Kaltin

AU - Martin, Karen

AU - Martyn, Adam

AU - Ranieri, Barbara

AU - White, Jo

AU - Jayde, Victoria

AU - Bowes, Leanne

AU - Mamers, Pamela

AU - Giles, Debra

AU - Hendley, Joy

AU - Alsop, Katherine

AU - Schmidt, Trudy

AU - Shirley, Helen

AU - Ball, Colleen

AU - Young, Cherry

AU - Viduka, Suzanna

AU - Tran, Hoa

AU - Bilic, Sanela

AU - Glavinas, Lydia

AU - Brooks, Julia

N1 - Funding Information: This project was supported by the National Health and Medical Research Council (NHMRC) of Australia (scholarship to B.G.), Cancer Institute New South Wales and Cancer Australia (552481). AdeF is funded by the University of Sydney Cancer Research Fund and the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre. We gratefully acknowledge the cooperation of the institutions that supported the study. We also acknowledge the contribution of Australian Ovarian Cancer Study Group (full list can be found at http://www.aocstudy.org), all study nurses and research assistants and would like to thank all of the women who participated in AOCS. AOCS was supported by U.S. Army Medical Research and Materiel Command DAMD17-01-1-0729, NHMRC Enabling Grant 400413 and Project Grant 400281, the Cancer Council Tasmania and the Cancer Foundation of Western Australia.

PY - 2014/5/9

Y1 - 2014/5/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84901049508&partnerID=8YFLogxK

U2 - 10.1038/srep04669

DO - 10.1038/srep04669

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 24810093

AN - SCOPUS:84901049508

SN - 2045-2322

VL - 4

JO - Scientific Reports

JF - Scientific Reports

M1 - 4669

ER -

Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

Abstract

Bibliographical note

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this