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Medical Oncology
Erschienen in: Medical Oncology 2/2013

01.06.2013 | Review Article

The significance of heat shock proteins in breast cancer therapy

verfasst von: Sevil Oskay Halacli, Burcin Halacli, Kadri Altundag

Erschienen in: Medical Oncology | Ausgabe 2/2013

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Abstract

The evalutionary conserved heat shock proteins are involved basically life protecting mechanisms against harmful extracellular effects such as primarily heat shock response. Normally, the expression of these proteins is increased for cellular adaptation to high temperature. This increase is also important in the etiology of breast cancer. Overexpression of heat shock proteins is associated with reduced disease-free survival in breast cancer. However, increased expression of these proteins is related to acquired resistance of traditional chemotherapeutic drugs in use in breast cancer treatment. In this review, we discuss the multiple roles of heatshock proteins in resistance and where we are to overcome this in clinical practice.
Literatur
1.
Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10:86–103.PubMedCrossRef
2.
Georgopoulos C, Welch WJ. Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol. 1993;9:601–34.PubMedCrossRef
3.
Hightower LE. Heat shock, stress proteins, chaperones, and proteotoxicity. Cell. 1991;66:191–7.PubMedCrossRef
4.
5.
Netzer WJ, Hartl FU. Protein folding in the cytosol: chaperonin-dependent and -independent mechanisms. Trends Biochem Sci. 1998;23:68–73.PubMedCrossRef
6.
Freeman BC, Yamamoto KR. Disassembly of transcriptional regulatory complexes by molecular chaperones. Science. 2002;296:2232–5.PubMedCrossRef
7.
Queitsch C, Sangster TA, Lindquist S. Hsp90 as a capacitor of phenotypic variation. Nature. 2002;417:618–24.PubMedCrossRef
8.
Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer. 2005;5:761–72.PubMedCrossRef
9.
O’Neill PA, et al. Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27. Br J Cancer. 2004;90:182–8.PubMedCrossRef
10.
Kim LS, Kim JH. Heat shock protein as molecular targets for breast cancer therapeutics. J Breast Cancer. 2011;14:167–74.PubMedCrossRef
11.
Kang SH, et al. Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability. BMC Cancer. 2008;8:286.PubMedCrossRef
12.
Hansen RK, et al. Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells. Breast Cancer Res Treat. 1999;56:187–96.PubMedCrossRef
13.
Oesterreich S, et al. The small heat shock protein hsp27 is correlated with growth and drug resistance in human breast cancer cell lines. Cancer Res. 1993;53:4443–8.PubMed
14.
Wei L, et al. Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial-mesenchymal transition and nuclear factor-kappaB. Breast Cancer Res. 2011;13:R101.PubMedCrossRef
15.
Shin KD, et al. Blocking tumor cell migration and invasion with biphenyl isoxazole derivative KRIBB3, a synthetic molecule that inhibits Hsp27 phosphorylation. J Biol Chem. 2005;280:41439–48.PubMedCrossRef
16.
Cayado-Gutierrez N, et al. Downregulation of Hsp27 (HSPB1) in MCF-7 human breast cancer cells induces upregulation of PTEN. Cell Stress Chaperones. 2013;18:243–9.PubMedCrossRef
17.
Straume O, et al. Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer. Proc Natl Acad Sci USA. 2012;109:8699–704.PubMedCrossRef
18.
Sarkar R, et al. Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast cancer cells by targeting heat shock proteins. Biochem Biophys Res Commun. 2012;427:80–5.PubMedCrossRef
19.
Sims JT, et al. Imatinib reverses doxorubicin resistance by affecting activation of STAT3-dependent NF-kappaB and HSP27/p38/AKT pathways and by inhibiting ABCB1. PLoS ONE. 2013;8:e55509.PubMedCrossRef
20.
Antoon JW, et al. Pharmacology and anti-tumor activity of RWJ67657, a novel inhibitor of p38 mitogen activated protein kinase. Am J Cancer Res. 2012;2:446–58.PubMed
21.
Lee CH, et al. Inhibition of heat shock protein (Hsp) 27 potentiates the suppressive effect of Hsp90 inhibitors in targeting breast cancer stem-like cells. Biochimie. 2012;94:1382–9.PubMedCrossRef
22.
Vargas-Roig LM, et al. Heat shock protein expression and drug resistance in breast cancer patients treated with induction chemotherapy. Int J Cancer. 1998;79:468–75.PubMedCrossRef
23.
Ciocca DR, et al. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst. 1993;85:570–4.PubMedCrossRef
24.
Hansen RK, et al. Quercetin inhibits heat shock protein induction but not heat shock factor DNA-binding in human breast carcinoma cells. Biochem Biophys Res Commun. 1997;239:851–6.PubMedCrossRef
25.
Nylandsted J, et al. Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2. Proc Natl Acad Sci USA. 2000;97:7871–6.PubMedCrossRef
26.
Nylandsted J, Brand K, Jaattela M. Heat shock protein 70 is required for the survival of cancer cells. Ann N Y Acad Sci. 2000;926:122–5.PubMedCrossRef
27.
Barnes JA, et al. Expression of inducible Hsp70 enhances the proliferation of MCF-7 breast cancer cells and protects against the cytotoxic effects of hyperthermia. Cell Stress Chaperones. 2001;6:316–25.PubMedCrossRef
28.
Kalogeraki A, et al. Correlation of heat shock protein (HSP70) expression with cell proliferation (MIB1), estrogen receptors (ER) and clinicopathological variables in invasive ductal breast carcinomas. J Exp Clin Cancer Res. 2007;26:367–8.PubMed
29.
Davidoff AM, Iglehart JD, Marks JR. Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. Proc Natl Acad Sci USA. 1992;89:3439–42.PubMedCrossRef
30.
Sims JD, McCready J, Jay DG. Extracellular heat shock protein (Hsp)70 and Hsp90alpha assist in matrix metalloproteinase-2 activation and breast cancer cell migration and invasion. PLoS ONE. 2011;6:e18848.PubMedCrossRef
31.
Chen CH, et al. Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. Cancer Res. 2000;60:1035–42.PubMed
32.
Kim JH, et al. Enhanced immunity by NeuEDhsp70 DNA vaccine Is needed to combat an aggressive spontaneous metastatic breast cancer. Mol Ther. 2005;11:941–9.PubMedCrossRef
33.
Hauser H, et al. Secretory heat-shock protein as a dendritic cell-targeting molecule: a new strategy to enhance the potency of genetic vaccines. Gene Ther. 2004;11:924–32.PubMedCrossRef
34.
Pakravan N, Soudi S, Hassan ZM. N-terminally fusion of Her2/neu to HSP70 decreases efficiency of Her2/neu DNA vaccine. Cell Stress Chaperones. 2010;15:631–8.PubMedCrossRef
35.
Cheng Q, et al. Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer. Breast Cancer Res. 2012;14:R62.PubMedCrossRef
36.
Pick E, et al. High HSP90 expression is associated with decreased survival in breast cancer. Cancer Res. 2007;67:2932–7.PubMedCrossRef
37.
Yano M, et al. Expression and roles of heat shock proteins in human breast cancer. Jpn J Cancer Res. 1996;87:908–15.PubMedCrossRef
38.
Giordano C, et al. Leptin increases HER2 protein levels through a STAT3-mediated up-regulation of Hsp90 in breast cancer cells. Mol Oncol. 2012;7891:123–8.
39.
El Hamidieh A, Grammatikakis N, Patsavoudi E. Cell surface Cdc37 participates in extracellular HSP90 mediated cancer cell invasion. PLoS ONE. 2012;7:e42722.PubMedCrossRef
40.
Yano M, et al. Expression of hsp90 and cyclin D1 in human breast cancer. Cancer Lett. 1999;137:45–51.PubMedCrossRef
41.
Kang SA, et al. Hsp90 rescues PTK6 from proteasomal degradation in breast cancer cells. Biochem J. 2012;447:313–20.PubMedCrossRef
42.
Zuo K, et al. Short-hairpin RNA-mediated Heat shock protein 90 gene silencing inhibits human breast cancer cell growth in vitro and in vivo. Biochem Biophys Res Commun. 2012;421:396–402.PubMedCrossRef
43.
Cooper LC, et al. Hsp90alpha/beta associates with the GSK3beta/axin1/phospho-beta-catenin complex in the human MCF-7 epithelial breast cancer model. Biochem Biophys Res Commun. 2011;413:550–4.PubMedCrossRef
44.
DeBoer C, et al. Geldanamycin, a new antibiotic. J Antibiot (Tokyo). 1970;23:442–7.CrossRef
45.
Prodromou C, et al. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell. 1997;90:65–75.PubMedCrossRef
46.
Taldone T, et al. Design, synthesis, and evaluation of small molecule Hsp90 probes. Bioorg Med Chem. 2011;19:2603–14.PubMedCrossRef
47.
Wang K, et al. Geldanamycin destabilizes HER2 tyrosine kinase and suppresses Wnt/beta-catenin signaling in HER2 overexpressing human breast cancer cells. Oncol Rep. 2007;17:89–96.PubMed
48.
Pedersen NM, et al. Geldanamycin-induced down-regulation of ErbB2 from the plasma membrane is clathrin dependent but proteasomal activity independent. Mol Cancer Res. 2008;6:491–500.PubMedCrossRef
49.
Mandler R, et al. Immunoconjugates of geldanamycin and anti-HER2 monoclonal antibodies: antiproliferative activity on human breast carcinoma cell lines. J Natl Cancer Inst. 2000;92:1573–81.PubMedCrossRef
50.
Supko JG, et al. Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother Pharmacol. 1995;36:305–15.PubMedCrossRef
51.
Schulte TW, Neckers LM. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother Pharmacol. 1998;42:273–9.PubMedCrossRef
52.
Schulz R, et al. Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression. J Exp Med. 2012;209:275–89.PubMedCrossRef
53.
Schulz R, Dobbelstein M, Moll UM. HSP90 inhibitor antagonizing MIF: the specifics of pleiotropic cancer drug candidates. Oncoimmunology. 2012;1:1425–6.PubMedCrossRef
54.
Rodrigues LM, et al. Effects of HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on NEU/HER2 overexpressing mammary tumours in MMTV-NEU-NT mice monitored by Magnetic Resonance Spectroscopy. BMC Res Notes. 2012;5:250.PubMedCrossRef
55.
Modi S, et al. HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res. 2011;17:5132–9.PubMedCrossRef
56.
Gartner EM, et al. A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer. Breast Cancer Res Treat. 2012;131:933–7.PubMedCrossRef
57.
Nowakowski GS, et al. A phase I trial of twice-weekly 17-allylamino-demethoxy-geldanamycin in patients with advanced cancer. Clin Cancer Res. 2006;12(20 Pt 1):6087–93.PubMedCrossRef
58.
Wong C, et al. AKT-aro and HER2-aro, models for de novo resistance to aromatase inhibitors; molecular characterization and inhibitor response studies. Breast Cancer Res Treat. 2012;134:671–81.PubMedCrossRef
59.
Jhaveri K, et al. A phase I dose-escalation trial of trastuzumab and alvespimycin hydrochloride (KOS-1022; 17 DMAG) in the treatment of advanced solid tumors. Clin Cancer Res. 2012;18:5090–8.PubMedCrossRef
60.
Aregbe AO, et al. Population pharmacokinetic analysis of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in adult patients with solid tumors. Cancer Chemother Pharmacol. 2012;70:201–5.PubMedCrossRef
61.
Jego G et al. Targeting heat shock proteins in cancer. 2010 Nov 13. [Epub ahead of print].
Metadaten
Titel
The significance of heat shock proteins in breast cancer therapy
verfasst von
Sevil Oskay Halacli
Burcin Halacli
Kadri Altundag
Publikationsdatum
01.06.2013
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2013
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0575-y

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