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Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells through up-regulation of p73

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Abstract

Recent gene expression profiling studies have identified five breast cancer subtypes, of which the basal-like subtype is the most aggressive. Basal-like breast cancer poses serious clinical challenges as there are currently no targeted therapies available to treat it. Although there is increasing evidence that these tumors possess specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and the development of drug resistance. To overcome this limitation, our goal was to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a validated kinase inhibitor library, we showed that inhibition of the mTOR, TGFβRI, NFκB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468 cells to cisplatin treatment. Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect of rapamycin plus cisplatin on basal-like breast cancer cells was mediated through the induction of p73. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects. In conclusion, combination therapy with mTOR inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of basal-like breast cancers.

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References

  1. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874. doi:10.1073/pnas.191367098

    Article  PubMed  CAS  Google Scholar 

  2. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100(14):8418–8423. doi:10.1073/pnas.0932692100

    Article  PubMed  CAS  Google Scholar 

  3. Leong CO, Vidnovic N, DeYoung MP, Sgroi D, Ellisen LW (2007) The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J Clin Invest 117(5):1370–1380. doi:10.1172/JCI30866

    Article  PubMed  CAS  Google Scholar 

  4. Lim LY, Vidnovic N, Ellisen LW, Leong CO (2009) Mutant p53 mediates survival of breast cancer cells. Br J Cancer 101(9):1606–1612. doi:10.1038/sj.bjc.6605335

    Article  PubMed  CAS  Google Scholar 

  5. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD (2005) Trastuzumab after adjuvant chemotherapy in her2-positive breast cancer. N Engl J Med 353(16):1659–1672. doi:10.1056/NEJMoa052306

    Article  PubMed  CAS  Google Scholar 

  6. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable her2-positive breast cancer. N Engl J Med 353(16):1673–1684. doi:10.1056/NEJMoa052122

    Article  PubMed  CAS  Google Scholar 

  7. Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, Bishop T, Benitez J, Rivas C, Bignon YJ, Chang-Claude J, Hamann U, Cornelisse CJ, Devilee P, Beckmann MW, Nestle-Kramling C, Daly PA, Haites N, Varley J, Lalloo F, Evans G, Maugard C, Meijers-Heijboer H, Klijn JG, Olah E, Gusterson BA, Pilotti S, Radice P, Scherneck S, Sobol H, Jacquemier J, Wagner T, Peto J, Stratton MR, McGuffog L, Easton DF (2005) Prediction of brca1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 11(14):5175–5180. doi:10.1158/1078-0432.CCR-04-2424

    Article  PubMed  CAS  Google Scholar 

  8. Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, Fatima A, Gelman RS, Ryan PD, Tung NM, De Nicolo A, Ganesan S, Miron A, Colin C, Sgroi DC, Ellisen LW, Winer EP, Garber JE (2010) Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol 28(7):1145–1153. doi:10.1200/JCO.2009.22.4725

    Article  PubMed  CAS  Google Scholar 

  9. Byrski T, Huzarski T, Dent R, Gronwald J, Zuziak D, Cybulski C, Kladny J, Gorski B, Lubinski J, Narod SA (2009) Response to neoadjuvant therapy with cisplatin in brca1-positive breast cancer patients. Breast Cancer Res Treat 115(2):359–363. doi:10.1007/s10549-008-0128-9

    Article  PubMed  CAS  Google Scholar 

  10. Rocco JW, Leong CO, Kuperwasser N, DeYoung MP, Ellisen LW (2006) P63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell 9(1):45–56. doi:10.1016/j.ccr.2005.12.013

    Article  PubMed  CAS  Google Scholar 

  11. Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27–55

    Article  PubMed  CAS  Google Scholar 

  12. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, Speed T, Spellman PT, DeVries S, Lapuk A, Wang NJ, Kuo WL, Stilwell JL, Pinkel D, Albertson DG, Waldman FM, McCormick F, Dickson RB, Johnson MD, Lippman M, Ethier S, Gazdar A, Gray JW (2006) A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10(6):515–527. doi:10.1016/j.ccr.2006.10.008

    Article  PubMed  CAS  Google Scholar 

  13. Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review. J Clin Oncol 26(15):2568–2581. doi:10.1200/JCO.2007.13.1748

    Article  PubMed  Google Scholar 

  14. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7:96. doi:10.1186/1471-2164-7-96

    Article  PubMed  Google Scholar 

  15. Yehiely F, Moyano JV, Evans JR, Nielsen TO, Cryns VL (2006) Deconstructing the molecular portrait of basal-like breast cancer. Trends Mol Med 12(11):537–544. doi:10.1016/j.molmed.2006.09.004

    Article  PubMed  CAS  Google Scholar 

  16. Sorlie T, Wang Y, Xiao C, Johnsen H, Naume B, Samaha RR, Borresen-Dale AL (2006) Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics 7:127. doi:10.1186/1471-2164-7-127

    Article  PubMed  Google Scholar 

  17. Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10(8):789–799. doi:10.1038/nm1087

    Article  PubMed  CAS  Google Scholar 

  18. Rosenbluth JM, Mays DJ, Pino MF, Tang LJ, Pietenpol JA (2008) A gene signature-based approach identifies mtor as a regulator of p73. Mol Cell Biol 28(19):5951–5964. doi:10.1128/MCB.00305-08

    Article  PubMed  CAS  Google Scholar 

  19. Gong JG, Costanzo A, Yang HQ, Melino G, Kaelin WG Jr, Levrero M, Wang JY (1999) The tyrosine kinase c-abl regulates p73 in apoptotic response to cisplatin-induced DNA damage. Nature 399(6738):806–809. doi:10.1038/21690

    Article  PubMed  CAS  Google Scholar 

  20. Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, Lu H, Kharbanda S, Weichselbaum R, Kufe D (1999) P73 is regulated by tyrosine kinase c-abl in the apoptotic response to DNA damage. Nature 399(6738):814–817. doi:10.1038/21704

    Article  PubMed  CAS  Google Scholar 

  21. Flinterman M, Guelen L, Ezzati-Nik S, Killick R, Melino G, Tominaga K, Mymryk JS, Gaken J, Tavassoli M (2005) E1a activates transcription of p73 and noxa to induce apoptosis. J Biol Chem 280(7):5945–5959. doi:10.1074/jbc.M406661200

    Article  PubMed  CAS  Google Scholar 

  22. Melino G, Bernassola F, Ranalli M, Yee K, Zong WX, Corazzari M, Knight RA, Green DR, Thompson C, Vousden KH (2004) P73 induces apoptosis via puma transactivation and bax mitochondrial translocation. J Biol Chem 279(9):8076–8083. doi:10.1074/jbc.M307469200

    Article  PubMed  CAS  Google Scholar 

  23. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374. doi:10.1158/1078-0432.CCR-04-0220

    Article  PubMed  CAS  Google Scholar 

  24. Turner NC, Reis-Filho JS (2006) Basal-like breast cancer and the brca1 phenotype. Oncogene 25(43):5846–5853. doi:10.1038/sj.onc.1209876

    Article  PubMed  CAS  Google Scholar 

  25. Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D, Savage K, Gillett CE, Schmitt FC, Ashworth A, Tutt AN (2007) Brca1 dysfunction in sporadic basal-like breast cancer. Oncogene 26(14):2126–2132. doi:10.1038/sj.onc.1210014

    Article  PubMed  CAS  Google Scholar 

  26. Ganesan S, Silver DP, Greenberg RA, Avni D, Drapkin R, Miron A, Mok SC, Randrianarison V, Brodie S, Salstrom J, Rasmussen TP, Klimke A, Marrese C, Marahrens Y, Deng CX, Feunteun J, Livingston DM (2002) Brca1 supports XIST RNA concentration on the inactive X chromosome. Cell 111(3):393–405. doi:S0092867402010528[pii]

    Article  PubMed  CAS  Google Scholar 

  27. Kriege M, Seynaeve C, Meijers-Heijboer H, Collee JM, Menke-Pluymers MB, Bartels CC, Tilanus-Linthorst MM, van den Ouweland A, van Geel B, Brekelmans CT, Klijn JG (2008) Distant disease-free interval, site of first relapse and post-relapse survival in brca1- and brca2-associated compared to sporadic breast cancer patients. Breast Cancer Res Treat 111(2):303–311. doi:10.1007/s10549-007-9781-7

    Article  PubMed  Google Scholar 

  28. Rakha EA, Reis-Filho JS, Ellis IO (2008) Impact of basal-like breast carcinoma determination for a more specific therapy. Pathobiology 75(2):95–103. doi:10.1159/000123847

    Article  PubMed  Google Scholar 

  29. Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S (2006) X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 9(2):121–132. doi:10.1016/j.ccr.2006.01.013

    Article  PubMed  CAS  Google Scholar 

  30. Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, Sledge GW, Carey LA (2008) Triple-negative breast cancer: risk factors to potential targets. Clin Cancer Res 14(24):8010–8018. doi:10.1158/1078-0432.CCR-08-1208

    Article  PubMed  CAS  Google Scholar 

  31. Tirkkonen M, Johannsson O, Agnarsson BA, Olsson H, Ingvarsson S, Karhu R, Tanner M, Isola J, Barkardottir RB, Borg A, Kallioniemi OP (1997) Distinct somatic genetic changes associated with tumor progression in carriers of brca1 and brca2 germ-line mutations. Cancer Res 57(7):1222–1227

    PubMed  CAS  Google Scholar 

  32. Foulkes WD, Brunet JS, Stefansson IM, Straume O, Chappuis PO, Begin LR, Hamel N, Goffin JR, Wong N, Trudel M, Kapusta L, Porter P, Akslen LA (2004) The prognostic implication of the basal-like (cyclin e high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of brca1-related breast cancer. Cancer Res 64(3):830–835

    Article  PubMed  CAS  Google Scholar 

  33. Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘brcaness’ in sporadic cancers. Nat Rev Cancer 4(10):814–819. doi:10.1038/nrc1457

    Article  PubMed  CAS  Google Scholar 

  34. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in brca mutant cells as a therapeutic strategy. Nature 434(7035):917–921. doi:10.1038/nature03445

    Article  PubMed  CAS  Google Scholar 

  35. Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP (2004) The role of brca1 in the cellular response to chemotherapy. J Natl Cancer Inst 96(22):1659–1668. doi:10.1093/jnci/djh312

    Article  PubMed  CAS  Google Scholar 

  36. Rakha EA, Ellis IO (2009) Triple-negative/basal-like breast cancer: review. Pathology 41(1):40–47. doi:10.1080/00313020802563510

    Article  PubMed  Google Scholar 

  37. Turner N, Tutt A, Ashworth A (2005) Targeting the DNA repair defect of brca tumours. Curr Opin Pharmacol 5(4):388–393. doi:10.1016/j.coph.2005.03.006

    Article  PubMed  CAS  Google Scholar 

  38. Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11(16):5678–5685. doi:10.1158/1078-0432.CCR-04-2421

    Article  PubMed  CAS  Google Scholar 

  39. Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M, Tsujimoto M, Yamoto M, Klein-Szanto AJ, Schilder RJ, Ohmichi M, Testa JR, Kimura T (2009) Mtor is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res 15(17):5404–5413. doi:10.1158/1078-0432.CCR-09-0365

    Article  PubMed  CAS  Google Scholar 

  40. Mabuchi S, Altomare DA, Cheung M, Zhang L, Poulikakos PI, Hensley HH, Schilder RJ, Ozols RF, Testa JR (2007) Rad001 inhibits human ovarian cancer cell proliferation, enhances cisplatin-induced apoptosis, and prolongs survival in an ovarian cancer model. Clin Cancer Res 13(14):4261–4270. doi:10.1158/1078-0432.CCR-06-2770

    Article  PubMed  CAS  Google Scholar 

  41. Zhang HY, Zhang PN, Sun H (2009) Aberration of the pi3k/akt/mtor signaling in epithelial ovarian cancer and its implication in cisplatin-based chemotherapy. Eur J Obstet Gynecol Reprod Biol 146(1):81–86. doi:10.1016/j.ejogrb.2009.04.035

    Article  PubMed  CAS  Google Scholar 

  42. Bae-Jump VL, Zhou C, Boggess JF, Gehrig PA (2009) Synergistic effect of rapamycin and cisplatin in endometrial cancer cells. Cancer 115(17):3887–3896. doi:10.1002/cncr.24431

    Article  PubMed  CAS  Google Scholar 

  43. Ekshyyan O, Rong Y, Rong X, Pattani KM, Abreo F, Caldito G, Chang JK, Ampil F, Glass J, Nathan CA (2009) Comparison of radiosensitizing effects of the mammalian target of rapamycin inhibitor cci-779 to cisplatin in experimental models of head and neck squamous cell carcinoma. Mol Cancer Ther 8(8):2255–2265. doi:10.1158/1535-7163.MCT-08-1184

    Article  PubMed  CAS  Google Scholar 

  44. Liu LZ, Zhou XD, Qian G, Shi X, Fang J, Jiang BH (2007) Akt1 amplification regulates cisplatin resistance in human lung cancer cells through the mammalian target of rapamycin/p70s6k1 pathway. Cancer Res 67(13):6325–6332. doi:10.1158/0008-5472.CAN-06-4261

    Article  PubMed  CAS  Google Scholar 

  45. Sinnberg T, Lasithiotakis K, Niessner H, Schittek B, Flaherty KT, Kulms D, Maczey E, Campos M, Gogel J, Garbe C, Meier F (2009) Inhibition of pi3k-akt-mtor signaling sensitizes melanoma cells to cisplatin and temozolomide. J Invest Dermatol 129(6):1500–1515. doi:10.1038/jid.2008.379

    Article  PubMed  CAS  Google Scholar 

  46. Tam KH, Yang ZF, Lau CK, Lam CT, Pang RW, Poon RT (2009) Inhibition of mtor enhances chemosensitivity in hepatocellular carcinoma. Cancer Lett 273(2):201–209. doi:10.1016/j.canlet.2008.08.018

    Article  PubMed  CAS  Google Scholar 

  47. Thallinger C, Poeppl W, Pratscher B, Mayerhofer M, Valent P, Tappeiner G, Joukhadar C (2007) Cci-779 plus cisplatin is highly effective against human melanoma in a scid mouse xenotranplantation model. Pharmacology 79(4):207–213. doi:10.1159/000101008

    Article  PubMed  CAS  Google Scholar 

  48. Beuvink I, Boulay A, Fumagalli S, Zilbermann F, Ruetz S, O’Reilly T, Natt F, Hall J, Lane HA, Thomas G (2005) The mtor inhibitor rad001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Cell 120(6):747–759. doi:10.1016/j.cell.2004.12.040

    Article  PubMed  CAS  Google Scholar 

  49. Wangpaichitr M, Wu C, You M, Kuo MT, Feun L, Lampidis T, Savaraj N (2008) Inhibition of mtor restores cisplatin sensitivity through down-regulation of growth and anti-apoptotic proteins. Eur J Pharmacol 591(1–3):124–127. doi:10.1016/j.ejphar.2008.06.028

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a grant from the MAKNA Cancer Research Award, Malaysia and e-Science Fund 02-02-09-SF0010 from the Ministry of Science, Technology and Innovation, Malaysia (to COL, RR and SKC); by the International Medical University (IMU) Research Fund (to KHT, BST and HLC); and by the IMU BPharm Research Training Program (to SWW, WYK, YCY, CHC, JYL, CYL, SIQ, CF, CC, and IS). No sponsors of this work had any role in the design or conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. School of Pharmacy and Health Sciences, International Medical University, 126 Jalan 19/155B, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

    Su Wei Wong, Kai Hung Tiong, Weng Yip Kong, Yuen Chee Yue, Choon Hooi Chua, Jae Ying Lim, Chai Yuin Lee, Sean I. Quah, Cindy Fow, Cyril Chung, Irene So, Boon Shing Tan, Heng Lungh Choo & Chee-Onn Leong

  2. School of Postgraduate Studies and Research, School of Pharmacy and Health Sciences, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

    Kai Hung Tiong, Boon Shing Tan, Heng Lungh Choo & Chee-Onn Leong

  3. Medical Genetics Laboratory, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

    Rozita Rosli

  4. Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Bandar Sungai Long, Selangor, Malaysia

    Soon-Keng Cheong

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Wong, S.W., Tiong, K.H., Kong, W.Y. et al. Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells through up-regulation of p73. Breast Cancer Res Treat 128, 301–313 (2011). https://doi.org/10.1007/s10549-010-1055-0

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