Skip to main content

Advertisement

SpringerLink
Log in

Upregulation of mucin4 in ER-positive/HER2-overexpressing breast cancer xenografts with acquired resistance to endocrine and HER2-targeted therapies

  • Preclinical Study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

We studied resistance to endocrine and HER2-targeted therapies using a xenograft model of estrogen receptor positive (ER)/HER2-overexpressing breast cancer. Here, we report a novel phenotype of drug resistance in this model. MCF7/HER2-18 xenografts were treated with endocrine therapy alone or in combination with lapatinib and trastuzumab (LT) to inhibit HER2. Archival tumor tissues were stained with hematoxylin and eosin and with mucicarmine. RNA extracted from tumors at early time points and late after acquired resistance were analyzed for mucin4 (MUC4) expression by microarray and quantitative reverse transcriptase-PCR. Protein expression of the MUC4, ER, and HER2 signaling pathways was measured by immunohistochemistry and western blotting. The combination of the potent anti-HER2 regimen LT with either tamoxifen (Tam + LT) or estrogen deprivation (ED + LT) can cause complete eradication of ER-positive/HER2-overexpressing tumors in mice. Tumors developing resistance to this combination, as well as those acquiring resistance to endocrine therapy alone, exhibited a distinct histological and molecular phenotype—a striking increase in mucin-filled vacuoles and upregulation of several mucins including MUC4. At the onset of resistance, MUC4 mRNA and protein were increased. These tumors also showed upregulation and reactivation of HER2 signaling, while losing ER protein and the estrogen-regulated gene progesterone receptor. Mucins are upregulated in a preclinical model of ER-positive/HER2-overexpressing breast cancer as resistance develops to the combination of endocrine and anti-HER2 therapy. These mucin-rich tumors reactivate the HER2 pathway and shift their molecular phenotype to become more ER-negative/HER2-positive.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Arpino G, Gutierrez C, Weiss H, Rimawi M, Massarweh S, Bharwani L, De Placido S, Osborne CK, Schiff R (2007) Treatment of human epidermal growth factor receptor 2-overexpressing breast cancer xenografts with multiagent HER-targeted therapy. J Natl Cancer Inst 99(9):694–705. doi:10.1093/jnci/djk151

    Article  PubMed  CAS  Google Scholar 

  2. Arpino G, Wiechmann L, Osborne CK, Schiff R (2008) Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: molecular mechanism and clinical implications for endocrine therapy resistance. Endocr Rev 29(2):217–233. doi:10.1210/er.2006-0045

    Article  PubMed  CAS  Google Scholar 

  3. Massarweh S, Osborne CK, Creighton CJ, Qin L, Tsimelzon A, Huang S, Weiss H, Rimawi M, Schiff R (2008) Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res 68(3):826–833. doi:10.1158/0008-5472.CAN-07-2707

    Article  PubMed  CAS  Google Scholar 

  4. Britton DJ, Hutcheson IR, Knowlden JM, Barrow D, Giles M, McClelland RA, Gee JM, Nicholson RI (2006) Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth. Breast Cancer Res Treat 96(2):131–146. doi:10.1007/s10549-005-9070-2

    Article  PubMed  CAS  Google Scholar 

  5. Knowlden JM, Hutcheson IR, Jones HE, Madden T, Gee JM, Harper ME, Barrow D, Wakeling AE, Nicholson RI (2003) Elevated levels of epidermal growth factor receptor/c-erbB2 heterodimers mediate an autocrine growth regulatory pathway in tamoxifen-resistant MCF-7 cells. Endocrinology 144(3):1032–1044

    Article  PubMed  CAS  Google Scholar 

  6. Leary AF, Drury S, Detre S, Pancholi S, Lykkesfeldt AE, Martin LA, Dowsett M, Johnston SR (2010) Lapatinib restores hormone sensitivity with differential effects on estrogen receptor signaling in cell models of human epidermal growth factor receptor 2-negative breast cancer with acquired endocrine resistance. Clin Cancer Res 16(5):1486–1497. doi:10.1158/1078-0432.CCR-09-1764

    Article  PubMed  CAS  Google Scholar 

  7. Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Janicke F, Miller WR, Evans DB, Dugan M, Brady C, Quebe-Fehling E, Borgs M (2001) Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 19(18):3808–3816

    PubMed  CAS  Google Scholar 

  8. Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O’Rourke L, Oliva C, Stein S, Pegram M (2009) Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 27(33):5538–5546. doi:10.1200/JCO.2009.23.3734

    Article  PubMed  CAS  Google Scholar 

  9. Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Revil C, Jones A (2009) Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 27(33):5529–5537. doi:10.1200/JCO.2008.20.6847

    Article  PubMed  CAS  Google Scholar 

  10. Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, Schiff R, Gutierrez C, Migliaccio I, Anagnostou VK, Rimm DL, Magill P, Sellers M (2011) Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study. Clin Cancer Res 17(5):1147–1159. doi:10.1158/1078-0432.CCR-10-1869

    Article  PubMed  CAS  Google Scholar 

  11. Massarweh S, Osborne CK, Jiang S, Wakeling AE, Rimawi M, Mohsin SK, Hilsenbeck S, Schiff R (2006) Mechanisms of tumor regression and resistance to estrogen deprivation and fulvestrant in a model of estrogen receptor-positive, HER-2/neu-positive breast cancer. Cancer Res 66(16):8266–8273. doi:10.1158/0008-5472.CAN-05-4045

    Article  PubMed  CAS  Google Scholar 

  12. Rimawi MF, Wiechmann LS, Wang YC, Huang C, Migliaccio I, Wu MF, Gutierrez C, Hilsenbeck SG, Arpino G, Massarweh S, Ward R, Soliz R, Osborne CK, Schiff R (2011) Reduced dose and intermittent treatment with lapatinib and trastuzumab for potent blockade of the HER pathway in HER-2/neu-overexpressing breast tumor xenografts. Clin Cancer Res 17:1351–1361

    Article  PubMed  Google Scholar 

  13. Benz CC, Scott GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM, Osborne CK (1992) Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat 24(2):85–95

    Article  PubMed  CAS  Google Scholar 

  14. Moniaux N, Varshney GC, Chauhan SC, Copin MC, Jain M, Wittel UA, Andrianifahanana M, Aubert JP, Batra SK (2004) Generation and characterization of anti-MUC4 monoclonal antibodies reactive with normal and cancer cells in humans. J Histochem Cytochem 52(2):253–261

    Article  PubMed  CAS  Google Scholar 

  15. Creighton CJ, Massarweh S, Huang S, Tsimelzon A, Hilsenbeck SG, Osborne CK, Shou J, Malorni L, Schiff R (2008) Development of resistance to targeted therapies transforms the clinically associated molecular profile subtype of breast tumor xenografts. Cancer Res 68(18):7493–7501. doi:10.1158/0008-5472.CAN-08-1404

    Article  PubMed  CAS  Google Scholar 

  16. Saldanha AJ (2004) Java Treeview—extensible visualization of microarray data. Bioinformatics 20(17):3246–3248. doi:10.1093/bioinformatics/bth349bth349

    Article  PubMed  CAS  Google Scholar 

  17. Hammerich-Hille S, Kaipparettu BA, Tsimelzon A, Creighton CJ, Jiang S, Polo JM, Melnick A, Meyer R, Oesterreich S (2010) SAFB1 mediates repression of immune regulators and apoptotic genes in breast cancer cells. J Biol Chem 285(6):3608–3616. doi:10.1074/jbc.M109.066431

    Article  PubMed  CAS  Google Scholar 

  18. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262

    Article  PubMed  CAS  Google Scholar 

  19. Tibes R, Qiu Y, Lu Y, Hennessy B, Andreeff M, Mills GB, Kornblau SM (2006) Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells. Mol Cancer Ther 5(10):2512–2521. doi:10.1158/1535-7163.MCT-06-0334

    Article  PubMed  CAS  Google Scholar 

  20. Shapiro SS, Wilk MB (1965) An analysis of variance test for normality (complete samples). Biometrika 52(3–4):591–611

    Google Scholar 

  21. Mann HB, Whitney DR (1947) On a test of whether one of two random variables is stochastically larger than the other. Ann Math Stat 18(1):50–60

    Article  Google Scholar 

  22. Team RDC (2010) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  23. Steinbrecher JS, Silverberg SG (1976) Signet-ring cell carcinoma of the breast. The mucinous variant of infiltrating lobular carcinoma? Cancer 37(2):828–840

    Article  PubMed  CAS  Google Scholar 

  24. Chaturvedi P, Singh AP, Chakraborty S, Chauhan SC, Bafna S, Meza JL, Singh PK, Hollingsworth MA, Mehta PP, Batra SK (2008) MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. Cancer Res 68(7):2065–2070. doi:10.1158/0008-5472.CAN-07-6041

    Article  PubMed  CAS  Google Scholar 

  25. Carraway KL, Perez A, Idris N, Jepson S, Arango M, Komatsu M, Haq B, Price-Schiavi SA, Zhang J, Carraway CA (2002) Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: to protect and to survive. Prog Nucleic Acid Res Mol Biol 71:149–185

    Article  PubMed  CAS  Google Scholar 

  26. Hollingsworth MA, Swanson BJ (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4(1):45–60. doi:10.1038/nrc1251nrc1251

    Article  PubMed  CAS  Google Scholar 

  27. Karg A, Dinc ZA, Basok O, Ucvet A (2006) MUC4 expression and its relation to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in non-small cell lung cancer (NSCLC). Pathol Res Pract 202(8):577–583. doi:10.1016/j.prp.2006.04.002

    Article  PubMed  Google Scholar 

  28. Kwon KY, Ro JY, Singhal N, Killen DE, Sienko A, Allen TC, Zander DS, Barrios R, Haque A, Cagle PT (2007) MUC4 expression in non-small cell lung carcinomas: relationship to tumor histology and patient survival. Arch Pathol Lab Med 131(4):593–598

    PubMed  CAS  Google Scholar 

  29. Tamada S, Shibahara H, Higashi M, Goto M, Batra SK, Imai K, Yonezawa S (2006) MUC4 is a novel prognostic factor of extrahepatic bile duct carcinoma. Clin Cancer Res 12(14 Pt 1):4257–4264. doi:10.1158/1078-0432.CCR-05-2814

    Article  PubMed  CAS  Google Scholar 

  30. Tsutsumida H, Goto M, Kitajima S, Kubota I, Hirotsu Y, Wakimoto J, Batra SK, Imai K, Yonezawa S (2007) MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma. Lung Cancer 55(2):195–203. doi:10.1016/j.lungcan.2006.10.013

    Article  PubMed  Google Scholar 

  31. Chauhan SC, Singh AP, Ruiz F, Johansson SL, Jain M, Smith LM, Moniaux N, Batra SK (2006) Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125). Mod Pathol 19(10):1386–1394. doi:10.1038/modpathol.3800646

    Article  PubMed  CAS  Google Scholar 

  32. Munro EG, Jain M, Oliva E, Kamal N, Lele SM, Lynch MP, Guo L, Fu K, Sharma P, Remmenga S, Growdon WB, Davis JS, Rueda BR, Batra SK (2009) Upregulation of MUC4 in cervical squamous cell carcinoma: pathologic significance. Int J Gynecol Pathol 28(2):127–133. doi:10.1097/PGP.0b013e318184f3e0

    Article  PubMed  Google Scholar 

  33. Singh AP, Chauhan SC, Bafna S, Johansson SL, Smith LM, Moniaux N, Lin MF, Batra SK (2006) Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas. Prostate 66(4):421–429. doi:10.1002/pros.20372

    Article  PubMed  CAS  Google Scholar 

  34. Miyahara N, Shoda J, Ishige K, Kawamoto T, Ueda T, Taki R, Ohkohchi N, Hyodo I, Thomas MB, Krishnamurthy S, Carraway KL, Irimura T (2008) MUC4 interacts with ErbB2 in human gallbladder carcinoma: potential pathobiological implications. Eur J Cancer 44(7):1048–1056. doi:10.1016/j.ejca.2008.03.007

    Article  PubMed  CAS  Google Scholar 

  35. Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H, Hollingsworth MA, Buchler MW, Aubert JP, Batra SK (2001) Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res 7(12):4033–4040

    PubMed  CAS  Google Scholar 

  36. Workman HC, Miller JK, Ingalla EQ, Kaur RP, Yamamoto DI, Beckett LA, Young LJ, Cardiff RD, Borowsky AD, Carraway KL, Sweeney C, Carraway KL 3rd (2009) The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells. Breast Cancer Res 11(5):R70. doi:10.1186/bcr2364

    Article  PubMed  Google Scholar 

  37. Workman HC, Sweeney C, Carraway KL 3rd (2009) The membrane mucin Muc4 inhibits apoptosis induced by multiple insults via ErbB2-dependent and ErbB2-independent mechanisms. Cancer Res 69(7):2845–2852. doi:10.1158/0008-5472.CAN-08-2089

    Article  PubMed  CAS  Google Scholar 

  38. Ramsauer VP, Pino V, Farooq A, Carothers Carraway CA, Salas PJ, Carraway KL (2006) Muc4–ErbB2 complex formation and signaling in polarized CACO-2 epithelial cells indicate that Muc4 acts as an unorthodox ligand for ErbB2. Mol Biol Cell 17(7):2931–2941. doi:10.1091/mbc.E05-09-0895

    Article  PubMed  CAS  Google Scholar 

  39. Yokoyama A, Shi BH, Kawai T, Konishi H, Andoh R, Tachikawa H, Ihara S, Fukui Y (2007) Muc4 is required for activation of ErbB2 in signet ring carcinoma cell lines. Biochem Biophys Res Commun 355(1):200–203. doi:10.1016/j.bbrc.2007.01.133

    Article  PubMed  CAS  Google Scholar 

  40. Carraway KL 3rd, Rossi EA, Komatsu M, Price-Schiavi SA, Huang D, Guy PM, Carvajal ME, Fregien N, Carraway CA, Carraway KL (1999) An intramembrane modulator of the ErbB2 receptor tyrosine kinase that potentiates neuregulin signaling. J Biol Chem 274(9):5263–5266

    Article  PubMed  CAS  Google Scholar 

  41. Funes M, Miller JK, Lai C, Carraway KL 3rd, Sweeney C (2006) The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3. J Biol Chem 281(28):19310–19319. doi:10.1074/jbc.M603225200

    Article  PubMed  CAS  Google Scholar 

  42. Nagy P, Friedlander E, Tanner M, Kapanen AI, Carraway KL, Isola J, Jovin TM (2005) Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res 65(2):473–482

    PubMed  CAS  Google Scholar 

  43. Price-Schiavi SA, Jepson S, Li P, Arango M, Rudland PS, Yee L, Carraway KL (2002) Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance. Int J Cancer 99(6):783–791. doi:10.1002/ijc.10410

    Article  PubMed  CAS  Google Scholar 

  44. Mejias-Luque R, Peiro S, Vincent A, Van Seuningen I, de Bolos C (2008) IL-6 induces MUC4 expression through gp130/STAT3 pathway in gastric cancer cell lines. Biochim Biophys Acta 1783(10):1728–1736. doi:10.1016/j.bbamcr.2008.05.020

    Article  PubMed  CAS  Google Scholar 

  45. Andrianifahanana M, Singh AP, Nemos C, Ponnusamy MP, Moniaux N, Mehta PP, Varshney GC, Batra SK (2007) IFN-gamma-induced expression of MUC4 in pancreatic cancer cells is mediated by STAT-1 upregulation: a novel mechanism for IFN-gamma response. Oncogene 26(51):7251–7261. doi:10.1038/sj.onc.1210532

    Article  PubMed  CAS  Google Scholar 

  46. Andrianifahanana M, Agrawal A, Singh AP, Moniaux N, van Seuningen I, Aubert JP, Meza J, Batra SK (2005) Synergistic induction of the MUC4 mucin gene by interferon-gamma and retinoic acid in human pancreatic tumour cells involves a reprogramming of signalling pathways. Oncogene 24(40):6143–6154. doi:10.1038/sj.onc.1208756

    Article  PubMed  CAS  Google Scholar 

  47. Damera G, Xia B, Ancha HR, Sachdev GP (2006) IL-9 modulated MUC4 gene and glycoprotein expression in airway epithelial cells. Biosci Rep 26(1):55–67. doi:10.1007/s10540-006-9000-5

    Article  PubMed  CAS  Google Scholar 

  48. Damera G, Xia B, Sachdev GP (2006) IL-4 induced MUC4 enhancement in respiratory epithelial cells in vitro is mediated through JAK-3 selective signaling. Respir Res 7:39. doi:10.1186/1465-9921-7-39

    Article  PubMed  Google Scholar 

  49. Perez A, Barco R, Fernandez I, Price-Schiavi SA, Carraway KL (2003) PEA3 transactivates the Muc4/sialomucin complex promoter in mammary epithelial and tumor cells. J Biol Chem 278(38):36942–36952. doi:10.1074/jbc.M300264200M300264200

    Article  PubMed  CAS  Google Scholar 

  50. Guo S, Sonenshein GE (2004) Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway. Mol Cell Biol 24(19):8681–8690. doi:10.1128/MCB.24.19.8681-8690.200424/19/8681

    Article  PubMed  CAS  Google Scholar 

  51. Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM, Lluch A, Gray JW, Brown PH, Hilsenbeck SG, Osborne CK, Mills GB, Lee AV, Schiff R (2010) Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res 12(3):R40. doi:10.1186/bcr2594

    Article  PubMed  Google Scholar 

  52. Moniaux N, Chaturvedi P, Varshney GC, Meza JL, Rodriguez-Sierra JF, Aubert JP, Batra SK (2007) Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells. Br J Cancer 97(3):345–357. doi:10.1038/sj.bjc.6603868

    Article  PubMed  CAS  Google Scholar 

  53. Ponnusamy MP, Singh AP, Jain M, Chakraborty S, Moniaux N, Batra SK (2008) MUC4 activates HER2 signalling and enhances the motility of human ovarian cancer cells. Br J Cancer 99(3):520–526. doi:10.1038/sj.bjc.6604517

    Article  PubMed  CAS  Google Scholar 

  54. Ponnusamy MP, Lakshmanan I, Jain M, Das S, Chakraborty S, Dey P, Batra SK (2010) MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cells. Oncogene. doi:10.1038/onc.2010.309

    PubMed  Google Scholar 

  55. Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, Schiff R (2004) Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst 96(12):926–935

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Rena Mao and the Baylor Breast Center Pathology Core, Robin Ward and Maria Fernanda Prigge for technical assistance, Dr. Susan Hilsenbeck for advice on statistical analysis, Dr. Gary Chamness for help with manuscript writing, and Dr. Kermit Carraway for scientific discussion. This study was supported by DOD Grant W81XWH-08-1-0264 (to A.C.C.) and NIH SPORE Grant P50CA058183 and Cancer Center Grant P30CA125123, the EIF/Lee Jeans Breast Cancer Research Program, Breast Cancer Research Foundation and Stand Up 2 Cancer (to C.K.O. and R.S.).

Disclosures

The experiments described in this study comply with the current laws of the country in which they were performed. The authors declare that they have no relevant conflict of interest.

Author information

Authors and Affiliations

  1. Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA

    Albert C. Chen, Mothaffar Rimawi, Catherine Huang, Yen-Chao Wang, M. Carolina Gutierrez, C. Kent Osborne & Rachel Schiff

  2. Dan L. Duncan Cancer Center, Baylor College of Medicine, 1 Baylor Plaza, MS 600, Houston, TX, 77030, USA

    Albert C. Chen, Mothaffar Rimawi, Chad J. Creighton, Catherine Huang, Yen-Chao Wang, M. Carolina Gutierrez, C. Kent Osborne & Rachel Schiff

  3. Department of Pathology, Baylor College of Medicine, Houston, TX, USA

    M. Carolina Gutierrez

  4. Translational Research Unit, Tuscany Tumor Institute, Prato, Italy

    Ilenia Migliaccio

  5. Instituto de Investigación Sanataria del Hospital Gregorio Marañón, Madrid, Spain

    Sara Lopez-Tarruella

  6. University of Kentucky and Markey Cancer Center, Lexington, KY, USA

    Suleiman Massarweh

  7. University of Nebraska Medical Center, Omaha, NE, USA

    Surinder K. Batra

  8. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    Albert C. Chen, C. Kent Osborne & Rachel Schiff

Authors
  1. Albert C. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilenia Migliaccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mothaffar Rimawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara Lopez-Tarruella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chad J. Creighton
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Suleiman Massarweh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Catherine Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yen-Chao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Surinder K. Batra
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Carolina Gutierrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C. Kent Osborne
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rachel Schiff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rachel Schiff.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, A.C., Migliaccio, I., Rimawi, M. et al. Upregulation of mucin4 in ER-positive/HER2-overexpressing breast cancer xenografts with acquired resistance to endocrine and HER2-targeted therapies. Breast Cancer Res Treat 134, 583–593 (2012). https://doi.org/10.1007/s10549-012-2082-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-012-2082-9

Keywords

Search

Navigation