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

B. Gao, A.J. Russell, J. Beesley, X. Chen, S.C. Healey, M.J. Henderson, M. Wong, C. Emmanuel, L. Galletta, S.E. Johnatty, D.D.L. Bowtell, M. Haber, M.D. Norris, P.R. Harnett, G. Chenevix-Trench, R.L. Balleine, A. Defazio, D.M. Gertig, A.C. Green, P.M. Webb & 150 others J. Hung, S. Moore, N. Traficante, S. Fereday, K. Harrap, T. Sadkowsky, N. Pandeya, R.C. Stuart- Harris, F. Kirsten, J. Rutovitz, P. Clingan, A. Glasgow, A.M. Proietto, S.G. Braye, G. Otton, J.B. Shannon, T. Bonaventura, J.A. Stewart, S.D. Begbie, M.L. Friedlander, D.R. Bell, S. Baron-Hay, A.J. Ferrier, G.B. Gard, D.F. Nevell, N. Pavlakis, S. Valmadre, B. Young, C. Camaris, R.L. Crouch, L.S. Edwards, N.F. Hacker, D.E. Marsden, G.M. Robertson, P.J. Beale, J.M. Beith, J. Carter, C. Dalrymple, A.L. Hamilton, R.S. Houghton, P. Russell, M.J. Links, J.G. Grygiel, J. Hill, A.H. Brand, K. Byth, R.C. Jaworski, R.K. Sharma, A. Achen, G.V. Wain, B.G. Ward, D.J. Papadimos, A.J. Crandon, M.C. Cummings, K. Horwood, A. Obermair, L.C. Perrin, D.K. Wyld, J.L. Nicklin, M.L.J. Davy, M.K. Oehler, C. Hall, T.J. Dodd, T. Healy, K.B. Pittman, D.W. Henderson, J. Miller, J. Pierdes, P.I. Blomfield, D.R. Challis, R. Mcintosh, A.J.C. Parker, B.D. Brown, R.M. Rome, D.G. Allen, P.T. Grant, S.E. Hyde, R. Laurie, M.J. Robbie, D.L. Healy, T.W. Jobling, T.P. Manolitsas, J. Mcnealage, P.A.W. Rogers, B.J. Susil, E. Sumithran, I.J. Simpson, K.A. Phillips, D. Rischin, S.B. Fox, D.S. Johnson, P.M. Waring, S. Lade, M.B. Loughrey, N. O'Callaghan, W.K. Murray, V.R. Billson, J.M. Pyman, D. Neesham, M.A. Quinn, C.R. Underhill, R.C.R.W. Bell, L. Ng, R. Blum, V. Ganju, Ian Hammond, Yee Leung, A.J. Mccartney, M. Buck, I. Haviv, D.M. Purdie, D.C. Whiteman, N. Zeps, M.R. Malt, A. Mellon, R.H. Robertson, T. Vanden Bergh, M. Jones, P. Mackenzie, J. Maidens, K. Nattress, Y. Chiew, A. Stenlake, H.W. Sullivan, B. Alexander, P. Ashover, S. Brown, T. Corrish, L. Green, L. Jackman, K. Ferguson, K.C. Martin, A.C. Martyn, B.A. Ranieri, J. White, V. Jayde, L. Bowes, P.M. Mamers, D. Giles, J. Hendley, K. Alsop, T. Schmidt, H. Shirley, C. Ball, C. Young, S. Viduka, H.N. Tran, S. Bilic, L. Glavinas, J. Brooks

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)4669-
    JournalScientific Reports
    Volume4
    DOIs
    Publication statusPublished - 2014

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    Paclitaxel
    Ovarian Neoplasms
    Single Nucleotide Polymorphism
    Adenosine Triphosphate
    Cell Line
    Disease-Free Survival
    Neoplasms
    Genotype
    Survival

    Cite this

    Gao, B., Russell, A. J., Beesley, J., Chen, X., Healey, S. C., Henderson, M. J., ... Brooks, J. (2014). Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer. Scientific Reports, 4, 4669-. https://doi.org/10.1038/srep04669
    Gao, B. ; Russell, A.J. ; Beesley, J. ; Chen, X. ; Healey, S.C. ; Henderson, M.J. ; Wong, M. ; Emmanuel, C. ; Galletta, L. ; Johnatty, S.E. ; Bowtell, D.D.L. ; Haber, M. ; Norris, M.D. ; Harnett, P.R. ; Chenevix-Trench, G. ; Balleine, R.L. ; Defazio, A. ; Gertig, D.M. ; Green, A.C. ; Webb, P.M. ; Hung, J. ; Moore, S. ; Traficante, N. ; Fereday, S. ; Harrap, K. ; Sadkowsky, T. ; Pandeya, N. ; Stuart- Harris, R.C. ; Kirsten, F. ; Rutovitz, J. ; Clingan, P. ; Glasgow, A. ; Proietto, A.M. ; Braye, S.G. ; Otton, G. ; Shannon, J.B. ; Bonaventura, T. ; Stewart, J.A. ; Begbie, S.D. ; Friedlander, M.L. ; Bell, D.R. ; Baron-Hay, S. ; Ferrier, A.J. ; Gard, G.B. ; Nevell, D.F. ; Pavlakis, N. ; Valmadre, S. ; Young, B. ; Camaris, C. ; Crouch, R.L. ; Edwards, L.S. ; Hacker, N.F. ; Marsden, D.E. ; Robertson, G.M. ; Beale, P.J. ; Beith, J.M. ; Carter, J. ; Dalrymple, C. ; Hamilton, A.L. ; Houghton, R.S. ; Russell, P. ; Links, M.J. ; Grygiel, J.G. ; Hill, J. ; Brand, A.H. ; Byth, K. ; Jaworski, R.C. ; Sharma, R.K. ; Achen, A. ; Wain, G.V. ; Ward, B.G. ; Papadimos, D.J. ; Crandon, A.J. ; Cummings, M.C. ; Horwood, K. ; Obermair, A. ; Perrin, L.C. ; Wyld, D.K. ; Nicklin, J.L. ; Davy, M.L.J. ; Oehler, M.K. ; Hall, C. ; Dodd, T.J. ; Healy, T. ; Pittman, K.B. ; Henderson, D.W. ; Miller, J. ; Pierdes, J. ; Blomfield, P.I. ; Challis, D.R. ; Mcintosh, R. ; Parker, A.J.C. ; Brown, B.D. ; Rome, R.M. ; Allen, D.G. ; Grant, P.T. ; Hyde, S.E. ; Laurie, R. ; Robbie, M.J. ; Healy, D.L. ; Jobling, T.W. ; Manolitsas, T.P. ; Mcnealage, J. ; Rogers, P.A.W. ; Susil, B.J. ; Sumithran, E. ; Simpson, I.J. ; Phillips, K.A. ; Rischin, D. ; Fox, S.B. ; Johnson, D.S. ; Waring, P.M. ; Lade, S. ; Loughrey, M.B. ; O'Callaghan, N. ; Murray, W.K. ; Billson, V.R. ; Pyman, J.M. ; Neesham, D. ; Quinn, M.A. ; Underhill, C.R. ; Bell, R.C.R.W. ; Ng, L. ; Blum, R. ; Ganju, V. ; Hammond, Ian ; Leung, Yee ; Mccartney, A.J. ; Buck, M. ; Haviv, I. ; Purdie, D.M. ; Whiteman, D.C. ; Zeps, N. ; Malt, M.R. ; Mellon, A. ; Robertson, R.H. ; Vanden Bergh, T. ; Jones, M. ; Mackenzie, P. ; Maidens, J. ; Nattress, K. ; Chiew, Y. ; Stenlake, A. ; Sullivan, H.W. ; Alexander, B. ; Ashover, P. ; Brown, S. ; Corrish, T. ; Green, L. ; Jackman, L. ; Ferguson, K. ; Martin, K.C. ; Martyn, A.C. ; Ranieri, B.A. ; White, J. ; Jayde, V. ; Bowes, L. ; Mamers, P.M. ; Giles, D. ; Hendley, J. ; Alsop, K. ; Schmidt, T. ; Shirley, H. ; Ball, C. ; Young, C. ; Viduka, S. ; Tran, H.N. ; Bilic, S. ; Glavinas, L. ; Brooks, J. / Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer. In: Scientific Reports. 2014 ; Vol. 4. pp. 4669-.
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    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 = "B. Gao and A.J. Russell and J. Beesley and X. Chen and S.C. Healey and M.J. Henderson and M. Wong and C. Emmanuel and L. Galletta and S.E. Johnatty and D.D.L. Bowtell and M. Haber and M.D. Norris and P.R. Harnett and G. Chenevix-Trench and R.L. Balleine and A. Defazio and D.M. Gertig and A.C. Green and P.M. Webb and J. Hung and S. Moore and N. Traficante and S. Fereday and K. Harrap and T. Sadkowsky and N. Pandeya and {Stuart- Harris}, R.C. and F. Kirsten and J. Rutovitz and P. Clingan and A. Glasgow and A.M. Proietto and S.G. Braye and G. Otton and J.B. Shannon and T. Bonaventura and J.A. Stewart and S.D. Begbie and M.L. Friedlander and D.R. Bell and S. Baron-Hay and A.J. Ferrier and G.B. Gard and D.F. Nevell and N. Pavlakis and S. Valmadre and B. Young and C. Camaris and R.L. Crouch and L.S. Edwards and N.F. Hacker and D.E. Marsden and G.M. Robertson and P.J. Beale and J.M. Beith and J. Carter and C. Dalrymple and A.L. Hamilton and R.S. Houghton and P. Russell and M.J. Links and J.G. Grygiel and J. Hill and A.H. Brand and K. Byth and R.C. Jaworski and R.K. Sharma and A. Achen and G.V. Wain and B.G. Ward and D.J. Papadimos and A.J. Crandon and M.C. Cummings and K. Horwood and A. Obermair and L.C. Perrin and D.K. Wyld and J.L. Nicklin and M.L.J. Davy and M.K. Oehler and C. Hall and T.J. Dodd and T. Healy and K.B. Pittman and D.W. Henderson and J. Miller and J. Pierdes and P.I. Blomfield and D.R. Challis and R. Mcintosh and A.J.C. Parker and B.D. Brown and R.M. Rome and D.G. Allen and P.T. Grant and S.E. Hyde and R. Laurie and M.J. Robbie and D.L. Healy and T.W. Jobling and T.P. Manolitsas and J. Mcnealage and P.A.W. Rogers and B.J. Susil and E. Sumithran and I.J. Simpson and K.A. Phillips and D. Rischin and S.B. Fox and D.S. Johnson and P.M. Waring and S. Lade and M.B. Loughrey and N. O'Callaghan and W.K. Murray and V.R. Billson and J.M. Pyman and D. Neesham and M.A. Quinn and C.R. Underhill and R.C.R.W. Bell and L. Ng and R. Blum and V. Ganju and Ian Hammond and Yee Leung and A.J. Mccartney and M. Buck and I. Haviv and D.M. Purdie and D.C. Whiteman and N. Zeps and M.R. Malt and A. Mellon and R.H. Robertson and {Vanden Bergh}, T. and M. Jones and P. Mackenzie and J. Maidens and K. Nattress and Y. Chiew and A. Stenlake and H.W. Sullivan and B. Alexander and P. Ashover and S. Brown and T. Corrish and L. Green and L. Jackman and K. Ferguson and K.C. Martin and A.C. Martyn and B.A. Ranieri and J. White and V. Jayde and L. Bowes and P.M. Mamers and D. Giles and J. Hendley and K. Alsop and T. Schmidt and H. Shirley and C. Ball and C. Young and S. Viduka and H.N. Tran and S. Bilic and L. Glavinas and J. Brooks",
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    doi = "10.1038/srep04669",
    language = "English",
    volume = "4",
    pages = "4669--",
    journal = "Scientific Reports",
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    Gao, B, Russell, AJ, Beesley, J, Chen, X, Healey, SC, Henderson, MJ, Wong, M, Emmanuel, C, Galletta, L, Johnatty, SE, Bowtell, DDL, Haber, M, Norris, MD, Harnett, PR, Chenevix-Trench, G, Balleine, RL, Defazio, A, Gertig, DM, Green, AC, Webb, PM, Hung, J, Moore, S, Traficante, N, Fereday, S, Harrap, K, Sadkowsky, T, Pandeya, N, Stuart- Harris, RC, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, AM, Braye, SG, Otton, G, Shannon, JB, Bonaventura, T, Stewart, JA, Begbie, SD, Friedlander, ML, Bell, DR, Baron-Hay, S, Ferrier, AJ, Gard, GB, Nevell, DF, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, RL, Edwards, LS, Hacker, NF, Marsden, DE, Robertson, GM, Beale, PJ, Beith, JM, Carter, J, Dalrymple, C, Hamilton, AL, Houghton, RS, Russell, P, Links, MJ, Grygiel, JG, Hill, J, Brand, AH, Byth, K, Jaworski, RC, Sharma, RK, Achen, A, Wain, GV, Ward, BG, Papadimos, DJ, Crandon, AJ, Cummings, MC, Horwood, K, Obermair, A, Perrin, LC, Wyld, DK, Nicklin, JL, Davy, MLJ, Oehler, MK, Hall, C, Dodd, TJ, Healy, T, Pittman, KB, Henderson, DW, Miller, J, Pierdes, J, Blomfield, PI, Challis, DR, Mcintosh, R, Parker, AJC, Brown, BD, Rome, RM, Allen, DG, Grant, PT, Hyde, SE, Laurie, R, Robbie, MJ, Healy, DL, Jobling, TW, Manolitsas, TP, Mcnealage, J, Rogers, PAW, Susil, BJ, Sumithran, E, Simpson, IJ, Phillips, KA, Rischin, D, Fox, SB, Johnson, DS, Waring, PM, Lade, S, Loughrey, MB, O'Callaghan, N, Murray, WK, Billson, VR, Pyman, JM, Neesham, D, Quinn, MA, Underhill, CR, Bell, RCRW, Ng, L, Blum, R, Ganju, V, Hammond, I, Leung, Y, Mccartney, AJ, Buck, M, Haviv, I, Purdie, DM, Whiteman, DC, Zeps, N, Malt, MR, Mellon, A, Robertson, RH, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, Y, Stenlake, A, Sullivan, HW, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, KC, Martyn, AC, Ranieri, BA, White, J, Jayde, V, Bowes, L, Mamers, PM, Giles, D, Hendley, J, Alsop, K, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, HN, 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, pp. 4669-. https://doi.org/10.1038/srep04669

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

    In: Scientific Reports, Vol. 4, 2014, p. 4669-.

    Research output: Contribution to journalArticle

    TY - JOUR

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

    AU - Gao, B.

    AU - Russell, A.J.

    AU - Beesley, J.

    AU - Chen, X.

    AU - Healey, S.C.

    AU - Henderson, M.J.

    AU - Wong, M.

    AU - Emmanuel, C.

    AU - Galletta, L.

    AU - Johnatty, S.E.

    AU - Bowtell, D.D.L.

    AU - Haber, M.

    AU - Norris, M.D.

    AU - Harnett, P.R.

    AU - Chenevix-Trench, G.

    AU - Balleine, R.L.

    AU - Defazio, A.

    AU - Gertig, D.M.

    AU - Green, A.C.

    AU - Webb, P.M.

    AU - Hung, J.

    AU - Moore, S.

    AU - Traficante, N.

    AU - Fereday, S.

    AU - Harrap, K.

    AU - Sadkowsky, T.

    AU - Pandeya, N.

    AU - Stuart- Harris, R.C.

    AU - Kirsten, F.

    AU - Rutovitz, J.

    AU - Clingan, P.

    AU - Glasgow, A.

    AU - Proietto, A.M.

    AU - Braye, S.G.

    AU - Otton, G.

    AU - Shannon, J.B.

    AU - Bonaventura, T.

    AU - Stewart, J.A.

    AU - Begbie, S.D.

    AU - Friedlander, M.L.

    AU - Bell, D.R.

    AU - Baron-Hay, S.

    AU - Ferrier, A.J.

    AU - Gard, G.B.

    AU - Nevell, D.F.

    AU - Pavlakis, N.

    AU - Valmadre, S.

    AU - Young, B.

    AU - Camaris, C.

    AU - Crouch, R.L.

    AU - Edwards, L.S.

    AU - Hacker, N.F.

    AU - Marsden, D.E.

    AU - Robertson, G.M.

    AU - Beale, P.J.

    AU - Beith, J.M.

    AU - Carter, J.

    AU - Dalrymple, C.

    AU - Hamilton, A.L.

    AU - Houghton, R.S.

    AU - Russell, P.

    AU - Links, M.J.

    AU - Grygiel, J.G.

    AU - Hill, J.

    AU - Brand, A.H.

    AU - Byth, K.

    AU - Jaworski, R.C.

    AU - Sharma, R.K.

    AU - Achen, A.

    AU - Wain, G.V.

    AU - Ward, B.G.

    AU - Papadimos, D.J.

    AU - Crandon, A.J.

    AU - Cummings, M.C.

    AU - Horwood, K.

    AU - Obermair, A.

    AU - Perrin, L.C.

    AU - Wyld, D.K.

    AU - Nicklin, J.L.

    AU - Davy, M.L.J.

    AU - Oehler, M.K.

    AU - Hall, C.

    AU - Dodd, T.J.

    AU - Healy, T.

    AU - Pittman, K.B.

    AU - Henderson, D.W.

    AU - Miller, J.

    AU - Pierdes, J.

    AU - Blomfield, P.I.

    AU - Challis, D.R.

    AU - Mcintosh, R.

    AU - Parker, A.J.C.

    AU - Brown, B.D.

    AU - Rome, R.M.

    AU - Allen, D.G.

    AU - Grant, P.T.

    AU - Hyde, S.E.

    AU - Laurie, R.

    AU - Robbie, M.J.

    AU - Healy, D.L.

    AU - Jobling, T.W.

    AU - Manolitsas, T.P.

    AU - Mcnealage, J.

    AU - Rogers, P.A.W.

    AU - Susil, B.J.

    AU - Sumithran, E.

    AU - Simpson, I.J.

    AU - Phillips, K.A.

    AU - Rischin, D.

    AU - Fox, S.B.

    AU - Johnson, D.S.

    AU - Waring, P.M.

    AU - Lade, S.

    AU - Loughrey, M.B.

    AU - O'Callaghan, N.

    AU - Murray, W.K.

    AU - Billson, V.R.

    AU - Pyman, J.M.

    AU - Neesham, D.

    AU - Quinn, M.A.

    AU - Underhill, C.R.

    AU - Bell, R.C.R.W.

    AU - Ng, L.

    AU - Blum, R.

    AU - Ganju, V.

    AU - Hammond, Ian

    AU - Leung, Yee

    AU - Mccartney, A.J.

    AU - Buck, M.

    AU - Haviv, I.

    AU - Purdie, D.M.

    AU - Whiteman, D.C.

    AU - Zeps, N.

    AU - Malt, M.R.

    AU - Mellon, A.

    AU - Robertson, R.H.

    AU - Vanden Bergh, T.

    AU - Jones, M.

    AU - Mackenzie, P.

    AU - Maidens, J.

    AU - Nattress, K.

    AU - Chiew, Y.

    AU - Stenlake, A.

    AU - Sullivan, H.W.

    AU - Alexander, B.

    AU - Ashover, P.

    AU - Brown, S.

    AU - Corrish, T.

    AU - Green, L.

    AU - Jackman, L.

    AU - Ferguson, K.

    AU - Martin, K.C.

    AU - Martyn, A.C.

    AU - Ranieri, B.A.

    AU - White, J.

    AU - Jayde, V.

    AU - Bowes, L.

    AU - Mamers, P.M.

    AU - Giles, D.

    AU - Hendley, J.

    AU - Alsop, K.

    AU - Schmidt, T.

    AU - Shirley, H.

    AU - Ball, C.

    AU - Young, C.

    AU - Viduka, S.

    AU - Tran, H.N.

    AU - Bilic, S.

    AU - Glavinas, L.

    AU - Brooks, J.

    PY - 2014

    Y1 - 2014

    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.

    U2 - 10.1038/srep04669

    DO - 10.1038/srep04669

    M3 - Article

    VL - 4

    SP - 4669-

    JO - Scientific Reports

    JF - Scientific Reports

    SN - 2045-2322

    ER -