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Targeting tumour-initiating cells to improve the cure rates for triple-negative breast cancer

Published online by Cambridge University Press:  26 July 2010

Anna L. Stratford ,
Kristen Reipas ,
Christopher Maxwell  and
Sandra E. Dunn
Anna L. Stratford
Affiliation:
Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, CanadaV5Z 4H4.
Kristen Reipas
Affiliation:
Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, CanadaV5Z 4H4.
Christopher Maxwell
Affiliation:
Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, CanadaV5Z 4H4.
Sandra E. Dunn*
Affiliation:
Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, CanadaV5Z 4H4.
*
*Corresponding author: Sandra E. Dunn, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, CanadaV5Z 4H4. E-mail: [email protected]
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Abstract

Tumour recurrence is one of the biggest challenges in breast cancer management because it affects 25–30% of women with breast cancer and the tumours are often incurable. Women with triple-negative breast cancer (TNBC – lacking expression of the oestrogen receptor, progesterone receptor and the receptor HER2/ERBB2) have the highest rates of early recurrence relative to other breast cancer subtypes. Early recurrence might be due to tumour-initiating cells (TICs), which are resistant to conventional therapies, can remain dormant and can subsequently give rise to secondary tumours. In breast cancer, TICs are identified by the cell-surface markers CD44+/CD24−/EpCAM+ and/or possess ALDH1 enzyme activity. This subpopulation has the ability to self-renew, grow as mammospheres and initiate tumour formation. Fuelling the problem of relapse is the fact that chemotherapy and radiation can induce or select for TICs; this was reported in preclinical models and more recently in women being treated for breast cancer. Thus, new therapeutic agents for TNBC are presently being sought to overcome this problem. Here we review the roles of receptor tyrosine kinases, signalling intermediates and transcription factors in sustaining the TIC subpopulation. Particular emphasis is placed on targeting these molecules in order to eliminate and/or prevent the induction of TICs and ultimately reduce the frequency of TNBC recurrence.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e22
Copyright
Copyright © Cambridge University Press 2010

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References

References

Publications

1Liedtke, C. et al. (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. Journal of Clinical Oncology 26, 1275-1281CrossRefGoogle ScholarPubMed
2Sorlie, T. et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proceedings of the National Academy of Sciences of the United States of America 98, 10869-10874CrossRefGoogle ScholarPubMed
3Dent, R. et al. (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clinical Cancer Research 13, 4429-4434CrossRefGoogle ScholarPubMed
4Phillips, T.M., McBride, W.H. and Pajonk, F. (2006) The response of CD24 − /low/CD44+ breast cancer-intiating cells to radiation. Journal of the National Cancer Institute 98, 1777-1785CrossRefGoogle ScholarPubMed
5Li, X. et al. (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. Journal of the National Cancer Institute 100, 672-679CrossRefGoogle ScholarPubMed
6Wicha, M.S., Liu, S. and Dontu, G. (2006) Cancer stem cells: an old idea – a paradigm shift. Cancer Research 66, 1883-1890CrossRefGoogle ScholarPubMed
7Al-Hajj, M. et al. (2003) Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 100, 3983-3988CrossRefGoogle ScholarPubMed
8Ponti, D. et al. (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Research 65, 5506-5511CrossRefGoogle ScholarPubMed
9Shackleton, M. et al. (2009) Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell 138, 822-829CrossRefGoogle ScholarPubMed
10Chuthapisith, S. et al. (2010) Breast cancer chemoresistance: emerging importance of cancer stem cells. Surgical Oncology 19, 27-32CrossRefGoogle ScholarPubMed
11Creighton, C.J. et al. (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proceedings of the National Academy of Sciences of the United States of America 106, 13820-13825CrossRefGoogle ScholarPubMed
12Dylla, S.J. et al. (2008) Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS one 3, e2428CrossRefGoogle ScholarPubMed
13Fillmore, C.M. and Kuperwasser, C. (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Research 10, R25CrossRefGoogle ScholarPubMed
14Marangoni, E. et al. (2009) CD44 targeting reduces tumour growth and prevents post-chemotherapy relapse of human breast cancer xenographs. British Journal of Cancer 100, 918-922CrossRefGoogle Scholar
15To, K. et al. (2010) YB-1 induces expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance. Cancer Research 70, 2840-2851CrossRefGoogle ScholarPubMed
16Jin, L. et al. (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nature Medicine 12, 1167-1174CrossRefGoogle ScholarPubMed
17Godar, S. et al. (2008) Growth-inhibitory and tumor-suppressive functions of p53 depend on its repression of CD44 expression. Cell 134, 62-73CrossRefGoogle ScholarPubMed
18Eriksson, M. et al. (2007) Oncolytic adenoviruses kill breast cancer initiating CD44 + CD24 − /low cells. Molecular Therapeutics 15, 2088-2093Google ScholarPubMed
19Stockmans, G. et al. (2008) Triple-negative breast cancer. Current Opinion in Oncology 20, 614-620CrossRefGoogle ScholarPubMed
20Tan, A.R. and Swain, S.M. (2008) Therapeutic strategies for triple-negative breast cancer. Practice of Oncology: Recent Advances 14, 343-351Google ScholarPubMed
21Charafe-Jauffret, E., Ginestier, C. and Birnbaum, D. (2009) Breast cancer stem cells: tools and models to rely on. BMC Cancer 9, 202-211CrossRefGoogle Scholar
22Nakshatri, H., Srour, E.F. and Badve, S. (2009) Breast cancer stem cells and intrinsic subtypes: controversies rage on. Current Stem Cell Research and Therapies 4, 50-60CrossRefGoogle Scholar
23Shipitsin, M. et al. (2007) Molecular definition of breast tumor heterogeneity. Cancer Cell 11, 259-273CrossRefGoogle ScholarPubMed
24Ginestier, C. et al. (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1, 555-567CrossRefGoogle Scholar
25Korkaya, H. et al. (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27, 6120-6130CrossRefGoogle ScholarPubMed
26Nalwoga, H. et al. (2010) Expression of aldehyde dehydrogenase 1 (ALDH1) is associated with basal-like markers and features of aggressive tumours in African breast cancer. British Journal of Cancer 102, 369-375CrossRefGoogle ScholarPubMed
27Dontu, G. and Wicha, M.S. (2005) Survival of mammary stem cells in suspension culture: implications for stem cell biology and neoplasia. Journal of Mammary Gland Biology and Neoplasia 10, 75-86CrossRefGoogle ScholarPubMed
28Finkbeiner, M.R. et al. (2009) Profiling YB-1 target genes uncovers a new mechanism for MET receptor regulation in normal and malignant human mammary cells. Oncogene 28, 1421-1431CrossRefGoogle ScholarPubMed
29Lim, E. et al. (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nature Medicine 15, 907-913CrossRefGoogle ScholarPubMed
30Asselin-Labat, M.L. et al. (2006) Steroid hormone receptor status of mouse mammary stem cells. Journal of the National Cancer Institute 98, 1011-1014CrossRefGoogle ScholarPubMed
31Eirew, P. et al. (2008) A method for quantifying normal human mammary epithelial cells with in vivo regenerative ability. Nature Medicine 14, 1384-1389CrossRefGoogle ScholarPubMed
32Stingl, J. et al. (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439, 993-997CrossRefGoogle ScholarPubMed
33Visvader, J.E. (2009) Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes and Development 23, 2563-2577CrossRefGoogle ScholarPubMed
34Wallgren, A., Silfverswärd, C. and Eklund, G. (1976) Prognostic factors in mammary carcinoma. Acta Radiologica: Therapy, Physics, Biology 15, 1-16Google ScholarPubMed
35Croker, A.K. et al. (2009) High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. Journal of Cellular and Molecular Medicine 13, 2236-2252CrossRefGoogle ScholarPubMed
36Sheridan, C. et al. (2006) CD44+/CD24− breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Research 8, R59CrossRefGoogle ScholarPubMed
37Abraham, B.K. et al. (2005) Prevelance of CD44+/CD24−/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clinical Cancer Research 11, 1154-1159CrossRefGoogle Scholar
38Liu, R. et al. (2007) The prognostic role of a gene signature from tumorigenic breast-cancer cells. New England Journal of Medicine 356, 217-226CrossRefGoogle ScholarPubMed
39Gupta, P.B. et al. (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138, 1-15CrossRefGoogle ScholarPubMed
40Pandit, T.S. et al. (2009) Lymphatic metastasis of breast cancer cells is associated with differential gene expression profiles that predict cancer stem cell-like properties and the ability to survive, establish and grow in a foreign environment. International Journal of Oncology 35, 297-308Google Scholar
41Stratford, A.L. et al. (2007) Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer providing a potential target for therapy. Breast Cancer Research 9, R61CrossRefGoogle ScholarPubMed
42Cheang, M.C.U. et al. (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clinical Cancer Research 14, 1368-1376CrossRefGoogle ScholarPubMed
43Marangoni, E. et al. (2007) A new model of patient tumor-derived breast cancer xenografts for preclinical assays. Clinical Cancer Research 13, 3989-3998CrossRefGoogle ScholarPubMed
44Farnie, G. et al. (2007) Novel cell culture technique for primary ductal carcinoma in situ: role of notch and epidermal growth factor receptor signaling pathways. Journal of the National Cancer Institute 99, 616-627CrossRefGoogle ScholarPubMed
45Di Leo, A. et al. (2008) Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. Journal of Clinical Oncology 26, 5544-5552CrossRefGoogle ScholarPubMed
46Finn, R.S. et al. (2009) Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib or placebo as first-line treatment in HER2-negative or unknown metastatic breast cancer. Journal of Clinical Oncology 27, 3908-3915CrossRefGoogle ScholarPubMed
47Green, M.D. et al. (2009) Gefitinib treatment in hormone-resistant and hormone receptor-negative advanced breast cancer. Annals of Oncology 20, 1813-1817CrossRefGoogle ScholarPubMed
48Polychronis, A. et al. (2005) Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial. Lancet Oncology 6, 383-391CrossRefGoogle ScholarPubMed
49Normanno, N. et al. (2008) Breast cancer cells with acquired resistance to EGFR tyrosine kinase inhibitor gefitinib show persistant activation of MAPK signaling. Breast Cancer Research and Treatment 112, 25-33CrossRefGoogle ScholarPubMed
50She, Q.-B. et al. (2003) Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3′-kinase/Akt pathway signaling. Clinical Cancer Research 9, 4340-4346Google ScholarPubMed
51Corkery, B. et al. (2009) Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Annals of Oncology 20, 862-867CrossRefGoogle ScholarPubMed
52Hoadley, K.A. et al. (2007) EGFR associated expression profiles vary with breast tumor subtype. BMC Genomics 8, 258CrossRefGoogle ScholarPubMed
53Oliveras-Ferraros, C. et al. (2008) Growth and molecular interactions of the anti-EGFR antibody Cetuximab and the DNA cross-linking agent cisplatin in gefitinib-resistant MDA-MB-468 cells: new prospects in the treatment of triple-negative/basal-like breast cancer. International Journal of Oncology 33, 1165-1176Google ScholarPubMed
54Nielsen, T. et al. (2004) Expression of the insulin-like growth factor-1 receptor and urokinase plasminogen activator in breast cancer is associated with poor survival: potential for intervention with 17 allylamino 17-demethoxy geldanamycin. Cancer Research 64, 286-291CrossRefGoogle Scholar
55Law, J.H. et al. (2008) Phosphorylated insulin-like growth factor-1/insulin receptor is present in all breast cancer subtypes and is related to poor survival. Cancer Research 68, 10238-10246CrossRefGoogle ScholarPubMed
56Klinakis, A. et al. (2009) Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. Proceedings of the National Academy of Sciences of the United States of America 106, 2359-2364CrossRefGoogle Scholar
57Carboni, J.M. et al. (2005) Tumor development by transgenic expression of a constitutively active insulin-like growth factor I receptor. Cancer Research 65, 3781-3787CrossRefGoogle ScholarPubMed
58Kim, H.-G. et al. (2007) Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-ĸB and snail. Molecular and Cellular Biology 27, 3165-3175CrossRefGoogle Scholar
59Moody, S.E. et al. (2005) The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell 8, 197-209CrossRefGoogle ScholarPubMed
60Jones, R.A. et al. (2009) Reversibility and recurrence of IGF-IR-induced mammary tumors. Oncogene 28, 2152-2162CrossRefGoogle ScholarPubMed
61Camp, R.L., Rimm, E.B. and Rimm, D.L. (1999) Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma. Cancer 86, 2259-22653.0.CO;2-2>CrossRefGoogle ScholarPubMed
62Ghoussoub, R.A. et al. (1998) Expression of c-met is a strong independent prognostic factor in breast carcinoma. Cancer 82, 1513-15203.0.CO;2-7>CrossRefGoogle Scholar
63Welm, A.L. et al. (2005) MET and MYC cooperate in mammary tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 102, 4324-4329CrossRefGoogle ScholarPubMed
64Orian-Rousseau, V. et al. (2002) CD44 is required for two consecutive steps in HGF/c-MET signaling. Genes and Development 16, 3074-3086CrossRefGoogle ScholarPubMed
65Graveel, C.R. et al. (2009) Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer. Proceedings of the National Academy of Sciences of the United States of America 106, 12909-12914CrossRefGoogle ScholarPubMed
66Ponzo, M.G. et al. (2009) Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. Proceedings of the National Academy of Sciences of the United States of America 106, 12903-12908CrossRefGoogle ScholarPubMed
67Comoglio, P., Giordano, S. and Trusolino, L. (2008) Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nature Reviews Drug Discovery 7, 504-516CrossRefGoogle ScholarPubMed
68Hines, S.J. et al. (1995) Coexpression of the c-kit and stem cell factor genes in breast carcinomas. Cell Growth & Differentiation 6, 769-779Google ScholarPubMed
69Tsuda, H. et al. (2005) Frequent KIT and epidermal growth factor receptor overexpressions in undifferentiated-type breast carcinomas with ‘stem-cell-like’ features. Cancer Science 96, 333-339CrossRefGoogle ScholarPubMed
70Levina, V. et al. (2010) Elimination of human lung cancer stem cells through targeting of the stem cell factor-c-kit autocrine signaling loop. Cancer Research 70, 338-346CrossRefGoogle ScholarPubMed
71Nielsen, T.O. et al. (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast cancer. Clinical Cancer Research 10, 5367-5374CrossRefGoogle Scholar
72Renouf, D.J., Wilson, L. and Blanke, C.D. (2009) Successes and challenges in translational research: the development of targeted for gastrointestinal stromal tumours. Clinical Cancer Research 15, 3908-3911CrossRefGoogle ScholarPubMed
73Heinrich, M.C. et al. (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. Journal of Clinical Oncology 21, 4342-4349CrossRefGoogle ScholarPubMed
74Zhou, J. et al. (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proceedings of the National Academy of Sciences of the United States of America 104, 16158-16163CrossRefGoogle ScholarPubMed
75Eralp, Y. et al. (2008) MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer. Annals of Oncology 19, 669-674CrossRefGoogle ScholarPubMed
76Chen, R.-H., Abate, C. and Blenis, J. (1993) Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase. Proceedings of the National Academy of Sciences of the United States of America 90, 10952-10956CrossRefGoogle ScholarPubMed
77Schouten, G.J. et al. (1997) IKappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase. EMBO Journal 16, 3133-3144CrossRefGoogle ScholarPubMed
78Joel, P.B. et al. (1998) pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167. Molecular and Cellular Biology 18, 1978-1984CrossRefGoogle ScholarPubMed
79Stratford, A.L. et al. (2008) Y-box binding protein-1 serine 102 is a downstream target of p90 ribosomal S6 kinase in basal-like breast cancer cells. Breast Cancer Research 10, R99CrossRefGoogle ScholarPubMed
80Shimamura, A. et al. (2000) Rsk1 mediates a MEK-MAP kinase cell survival signal. Current Biology 10, 127-135CrossRefGoogle ScholarPubMed
81Anjum, R. et al. (2005) The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Current Biology 15, 1762-1767CrossRefGoogle ScholarPubMed
82Larrea, M.D. et al. (2009) RSK1 drives p17Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility. Proceedings of the National Academy of Sciences of the United States of America 106, 9268-9273CrossRefGoogle Scholar
83Clark, D.E. et al. (2005) The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation. Cancer Research 65, 3108-3116CrossRefGoogle ScholarPubMed
84Cuadrado, A. and Nebreda, A.R. (2007) New insights into RSK activation and hematopoietic cancer. Cancer Cell 12, 187-189CrossRefGoogle ScholarPubMed
85Smith, J.A. et al. (2005) Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer Research 65, 1027-1034CrossRefGoogle ScholarPubMed
86Xian, W. et al. (2009) Fibroblast growth factor receptor 1-transformed mammary epithelial cells are dependent on RSK activity for growth and survival. Cancer Research 69, 2244-2251CrossRefGoogle ScholarPubMed
87Cho, Y.-Y. et al. (2007) Ribosomal S6 kinase 2 is a key regulator in tumor promoter-induced cell transformation. Cancer Research 67, 8104-8112CrossRefGoogle ScholarPubMed
88Sapkota, G.P. et al. (2007) BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Journal of Biochemistry 401, 29-38CrossRefGoogle ScholarPubMed
89Cohen, M.S., Hadjivassiliou, H. and Taunton, J. (2007) A clickable inhibitor reveals context-dependent autoactivation of p90 RSK. Nature Chemical Biology 3, 156-160CrossRefGoogle ScholarPubMed
90Kleer, C.G. et al. (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 100, 11606-11611CrossRefGoogle ScholarPubMed
91Suvà, M.-L. et al. (2009) EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Research 69, 9211-9218CrossRefGoogle ScholarPubMed
92Gonzalez, M.E. et al. (2009) Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1. Oncogene 28, 843-853CrossRefGoogle ScholarPubMed
93Bergmann, S. et al. (2005) YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification. Cancer Research 65, 4078-4087CrossRefGoogle ScholarPubMed
94Bargou, R.C. et al. (1997) Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nature Medicine 3, 447-450CrossRefGoogle ScholarPubMed
95Kuwano, M. et al. (2003) The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies. Cancer Science 94, 9-14CrossRefGoogle ScholarPubMed
96Sutherland, B.W. et al. (2005) Akt phosphorylates the Y-box binding 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells. Oncogene 24, 4281-4292CrossRefGoogle ScholarPubMed
97Sakura, H. et al. (1988) Two human genes isolated by a novel method encode DNA-binding proteins containing a common region of homology. Gene 73, 499-507Google ScholarPubMed
98Wu, J. et al. (2006) Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2. Cancer Research 66, 4872-4879CrossRefGoogle ScholarPubMed
99Astanehe, A. et al. (2009) The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1. Oncogene 28, 2406-2418CrossRefGoogle ScholarPubMed
100Habibi, G. et al. (2008) Re-defining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease specific survival than estrogen receptor or HER-2 across all tumor subtypes. Breast Cancer Research 10, R86CrossRefGoogle ScholarPubMed
101Lee, C. et al. (2008) Targeting YB-1 in HER-2 over-expressing breast cancer cells induces apoptosis via the mTOR/STAT3 pathway and suppresses tumor growth in mice. Cancer Research 68, 8661-8666CrossRefGoogle Scholar
102Judge, A.D. et al. (2009) Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice. Journal of Clinical Investigation 119, 661-673CrossRefGoogle ScholarPubMed
103Semple, S.C. et al. (2010) Rational design of cationic lipids for siRNA delivery. Nature Biotechnology 28, 172-176CrossRefGoogle ScholarPubMed
104Narod, S.A. and Foulkes, W.D. (2004) BRCA1 and BRCA2: 1994 and beyond. Nature Reviews Cancer 4, 665-676CrossRefGoogle ScholarPubMed
105Stefansson, O.A. et al. (2009) Genomic profiling of breast tumours in relation to BRCA abnormalities and phenotypes. Breast Cancer Research 11, R47CrossRefGoogle ScholarPubMed
106Foulkes, W.D. (2004) BRCA1 functions as a breast stem cell regulator. Journal of Medical Genetics 41, 1-5CrossRefGoogle ScholarPubMed
107Bane, A.L. et al. (2007) BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. American Journal of Surgical Pathology 31, 121-128CrossRefGoogle ScholarPubMed
108Waddell, N. et al. (2009) Subtypes of familial breast tumours revealed by expression and copy number profiling. Breast Cancer Research and Treatment Dec 4; [Epub ahead of print]Google Scholar
109Turner, N.C. and Reis-Filho, J.S. (2006) Basal-like breast cancer and BRCA1 phenotype. Oncogene 25, 5846-5853CrossRefGoogle ScholarPubMed
110McCarthy, A. et al. (2007) A mouse model of basal-like breast carcinoma with metaplastic elements. Journal of Pathology 211, 389-398CrossRefGoogle ScholarPubMed
111Deng, C.X. and Wang, R.H. (2003) Roles of BRCA1 in DNA damage repair: a link between development and cancer. Human Molecular Genetics 12 Spec No 1, R113-R123CrossRefGoogle ScholarPubMed
112Bryant, H.E. et al. (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913-917CrossRefGoogle ScholarPubMed
113Farmer, H. et al. (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917-921CrossRefGoogle ScholarPubMed
114Evers, B. et al. (2008) Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin. Clinical Cancer Research 14, 3916-3925CrossRefGoogle ScholarPubMed
115Rottenberg, S. et al. (2008) High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proceedings of the National Academy of Sciences of the United States of America 105, 17079-17084CrossRefGoogle Scholar
116Byrski, T. et al. (2009) Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. Journal of Clinical Oncology 28, 375-379CrossRefGoogle ScholarPubMed
117Carey, L.A. (2010) Targeted chemotherapy? Platinum in BRCA1-dysfuntional breast cancer. Journal of Clinical Oncology 28, 361-363CrossRefGoogle ScholarPubMed
118Evers, B. et al. (2010) A high-throughput pharmaceutical screen identifies compounds with specific toxicity against BRCA2-deficient tumors. Clinical Cancer Research 16, 99-108CrossRefGoogle ScholarPubMed
119Fong, P.C. et al. (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. New England Journal of Medicine 361, 123-134CrossRefGoogle ScholarPubMed
120Furuta, S. et al. (2005) Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 102, 9176-9181CrossRefGoogle ScholarPubMed
121Liu, S. et al. (2008) BRCA1 regulates human mammary stem/progenitor cell fate. Proceedings of the National Academy of Sciences of the United States of America 105, 1680-1685CrossRefGoogle ScholarPubMed
122Ginestier, C., Liu, S. and Wicha, M.S. (2009) Getting to the root of BRCA1-deficient breast cancer. Cell Stem Cell 5, 229-230CrossRefGoogle Scholar
123Gautschi, O. et al. (2008) Aurora kinases as anticancer drug targets. Clinical Cancer Research 14, 1639-1648CrossRefGoogle ScholarPubMed
124Chang, S. et al. (2009) Expression of human BRCA1 variants in mouse ES cells allows functional analysis of BRCA1 mutations. Journal of Clinical Investigation 119, 3160-3171CrossRefGoogle ScholarPubMed
125Ouchi, M. et al. (2004) BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition. Journal of Biological Chemistry 279, 19643-19648CrossRefGoogle ScholarPubMed
126Sankaran, S. et al. (2007) Aurora-A kinase regulates breast cancer associated gene 1 inhibition of centrosome-dependent microtubule nucleation. Cancer Research 67, 11186-11194CrossRefGoogle ScholarPubMed
127Hennessy, B.T. et al. (2009) Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Research 69, 4116-4124CrossRefGoogle ScholarPubMed
128Honeth, G. et al. (2008) The CD44+/CD24− phenotype is enriched in basal-like breast tumors. Breast Cancer Research 10, R53CrossRefGoogle ScholarPubMed
129Tanei, T. et al. (2009) Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancer. Clinical Cancer Research 15, 4234-4241CrossRefGoogle Scholar
130Kai, K. et al. (2010) Breast cancer stem cells. Breast Cancer 17, 80-85CrossRefGoogle ScholarPubMed
131Sleeman, J.P. and Cremers, N. (2007) New concepts in breast cancer metastasis: tumour initiating cells and the microenvironment. Clinical and Experimental Metastasis 24, 707-715CrossRefGoogle ScholarPubMed
Stockmans, G. et al. (2008) Triple-negative breast cancer. Current Opinions in Oncology 20, 614-620CrossRefGoogle ScholarPubMed
Tan, A.R. and Swain, S.M. (2008) Therapeutic strategies for triple-negative breast cancer. The Cancer Journal 14, 343-351CrossRefGoogle ScholarPubMed
Visvader, J.E. (2009) Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes and Development 23, 2563-2577CrossRefGoogle ScholarPubMed
Shipitsin, M. and Polyak, K. (2008) The cancer stem cell hypothesis: in search of definitions, markers and relevance. Laboratory Investigation 88, 459-463CrossRefGoogle ScholarPubMed
Kai, K., Arima, Y., Kamiya, T. and Saya, H. (2010) Breast cancer stem cells. Breast Cancer 17, 80-85CrossRefGoogle ScholarPubMed
Diamandis, P. et al. (2007) Chemical genetics reveals a complex functional ground state of neural stem cells. Nature Chemical Biology 3, 268-273CrossRefGoogle ScholarPubMed
Stockmans, G. et al. (2008) Triple-negative breast cancer. Current Opinions in Oncology 20, 614-620CrossRefGoogle ScholarPubMed
Tan, A.R. and Swain, S.M. (2008) Therapeutic strategies for triple-negative breast cancer. The Cancer Journal 14, 343-351CrossRefGoogle ScholarPubMed
Visvader, J.E. (2009) Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes and Development 23, 2563-2577CrossRefGoogle ScholarPubMed
Shipitsin, M. and Polyak, K. (2008) The cancer stem cell hypothesis: in search of definitions, markers and relevance. Laboratory Investigation 88, 459-463CrossRefGoogle ScholarPubMed
Kai, K., Arima, Y., Kamiya, T. and Saya, H. (2010) Breast cancer stem cells. Breast Cancer 17, 80-85CrossRefGoogle ScholarPubMed
Diamandis, P. et al. (2007) Chemical genetics reveals a complex functional ground state of neural stem cells. Nature Chemical Biology 3, 268-273CrossRefGoogle ScholarPubMed