Cell Stress and Chaperones

, Volume 13, Issue 3, pp 253–262 | Cite as

Heat shock proteins in animal neoplasms and human tumours—a comparison

  • Mariarita Romanucci
  • Tania Bastow
  • Leonardo Della SaldaEmail author
Mini Review


Heat shock proteins (HSPs) are implicated in all phases of cancer from proliferation, impaired apoptosis and sustained angiogenesis to invasion and metastasis. The presence of abnormal HSP levels in several human tumours suggests that these proteins could be used as diagnostic and/or prognostic markers, whilst the direct correlation between HSP expression and drug resistance in neoplastic tissues means they could also be used to predict cancer response to specific treatment. HSPs have also been successfully targeted in clinical trials modifying their expression or chaperone activity. Preliminary studies in veterinary medicine have also demonstrated the presence of altered HSP expression in neoplasms, and the study of carcinogenesis and the role of HSPs in animal models will surely be an additional source of information for clinical cancer research.


Heat shock protein Cancer Animal HSP Stress protein Neoplasia 


  1. Abe M, Manola JB, Oh WK, Parslow DL, George DJ, Austin CL, Kantoff PW (2004) Plasma levels of heat shock protein 70 in patients with prostate cancer: a potential biomarker for prostate cancer. Clin Prostate Cancer 3:49–53PubMedGoogle Scholar
  2. Agoff SN, Hou J, Linzer DI, Wu B (1993) Regulation of the human hsp70 promoter by p53. Science 259:84–87PubMedGoogle Scholar
  3. Agueli C, Geraci F, Giudice G, Cimenti L, Cascino D, Sconzo G (2001) A constitutive 70 kDa heat shock protein is localized on the fibres of spindles and asters at metaphase in an ATP-dependent manner: a new role is proposed. Biochem J 360:413–419PubMedGoogle Scholar
  4. Ahern TE, Bird RC, Bird AC, Wolfe LG (1996) Expression of the oncogene c-erbB-2 in canine mammary cancers and tumour-derived cell lines. Am J Vet Res 57:693–696PubMedGoogle Scholar
  5. Akakura S, Yoshida M, Yoneda Y, Horinouchi S (2001) A role for Hsc70 in regulating nucleocytoplasmic transport of a temperature-sensitive p53 (p53Val-135). J Biol Chem 276:14649–14657PubMedGoogle Scholar
  6. Bagatell R, Paine-Murrieta GD, Taylor CW, Pulcini EJ, Akinaga S, Benjamin IJ, Whitesell L (2000) Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of Hsp90-binding agents. Clin Cancer Res 6:3312–3318PubMedGoogle Scholar
  7. Banerji U, O’Donnell A, Scurr M et al (2005) Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J Clin Oncol 23:4152–4161PubMedGoogle Scholar
  8. Barker CR, McNamara AV, Rackstraw SA, Nelson DE, Whire MR, Watson AJM, Jenkins JR (2006) Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage. Nucleic Acids Res 34:1148–1157PubMedGoogle Scholar
  9. Bausero MA, Bharti A, Page DT et al (2006) Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell. Tumour Biol 27:17–26PubMedGoogle Scholar
  10. Bisht KS, Bradbury CM, Mattson D et al (2003) Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. Cancer Res 63:8984–8995PubMedGoogle Scholar
  11. Brown CR, Doxsey SJ, Hong-Brown LQ, Martin RL, Welch WJ (1996a) Molecular chaperones and the centrosome. A role for TCP-1 in microtubule nucleation. J Biol Chem 271:824–832PubMedGoogle Scholar
  12. Brown CR, Hong-Brown LQ, Doxsey SJ, Welch WJ (1996b) Molecular chaperones and the centrosome. A role for Hsp 73 in centrosomal repair following heat shock treatment. J Biol Chem 271:833–840PubMedGoogle Scholar
  13. Bull EE, Dote H, Brady KJ et al (2004) Enhanced tumor cell radiosensitivity and abrogation of G2 and S phase arrest by the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin. Clin Cancer Res 10:8077–8084PubMedGoogle Scholar
  14. Calderwood SK (2005) Regulatory interfaces between the stress protein response and other gene expression programs in the cell. Methods 35:139–148PubMedGoogle Scholar
  15. Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172PubMedGoogle Scholar
  16. Cardoso F, Di Leo A, Larsimont D et al (2001) Evaluation of HER2, p53, bcl-2, topoisomerase II-alpha, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes. Ann Oncol 12:615–620PubMedGoogle Scholar
  17. Chae H, Yun J, Shin DY (2005) Transcription repression of a CCAAT-binding transcription factor CBF/HSP70 by p53. Exp Mol Med 37:488–491PubMedGoogle Scholar
  18. Cheung J, Smith DF (2000) Molecular chaperone interactions with steroid receptors: an update. Mol Endocrinol 14(7):939–946PubMedGoogle Scholar
  19. Chu RM, Sun TJ, Yang HY, Wang DG, Liao KW, Chuang TF, Li CH, Lee WC (2001) Heat shock proteins in canine transmissible venereal tumor. Vet Immunol Immunopathol 82:9–21PubMedGoogle Scholar
  20. Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103PubMedGoogle Scholar
  21. Ciocca DR, Clark GM, Tandon AK, Fuqua SAW, Welch WJ, McGuire WL (1993a) Heat shock protein Hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst 85:570–574PubMedGoogle Scholar
  22. Ciocca DR, Oesterreich S, Chamness GC, McGuire WL, Fuqua SAW (1993b) Biological and clinical implications of heat shock protein 27000 (Hsp27): a review. J Natl Cancer Inst 85:1558–1570PubMedGoogle Scholar
  23. Ciocca DR, Green S, Elledge RM et al (1998) Heat shock proteins hsp27 and hsp70: lack of correlation with response to tamoxifen and clinical course of disease in estrogen receptor-positive metastatic breast cancer (A Southwest Oncology Group Study). Clin Cancer Res 5:1263–1266Google Scholar
  24. Conroy SE, Latchman DS (1996) Do heat shock proteins have a role in breast cancer? Br J Cancer 74:717–721PubMedGoogle Scholar
  25. Conroy SE, Sasieni PD, Amin V, Wang DY, Smith P, Fentiman IS, Latchman DS (1998a) Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer. Br J Cancer 77:1875–1879PubMedGoogle Scholar
  26. Conroy SE, Sasieni PD, Fentiman I, Latchman DS (1998b) Autoantibodies to the 90 kDa heat shock protein and poor survival in breast cancer patients. Eur J Cancer 34:942–943PubMedGoogle Scholar
  27. de Carcer G (2004) Heat shock protein 90 regulates the metaphase–anaphase transition in a polo-like kinase-dependent manner. Cancer Res 64:5106–5112PubMedGoogle Scholar
  28. de Carcer G, do Carmo Avides M, Lallena MJ, Glover DM, Gonzalez G (2001) Requirement of Hsp90 for centrosomal function reflects its regulation of Polo kinase stability. EMBO J 20:2878–2884PubMedGoogle Scholar
  29. Didelot C, Schmitt E, Brunet M, Maingret L, Parcellier A, Garrido C (2006) Heat shock proteins: endogenous modulators of apoptotic cell death. Handb Exp Pharmacol 172:171–198PubMedGoogle Scholar
  30. Donnay I, Rauis J, Wouters-Ballman P, Devleschouwer N, Leclerq G, Versteegen JP (1993) Receptors for estrogen, progesterone and epidermal growth factors in normal and tumorous canine mammary tissues. J Reprod Fertil Suppl 47:501–512PubMedGoogle Scholar
  31. Dutra AP, Grana NV, Schmitt FC, Cassali GD (2004) c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors. Braz J Med Biol Res 37:1673–1681PubMedGoogle Scholar
  32. Eiseman JL, Lan J, Lagattuta TF, Hamburger DR, Joseph E, Covey JM, Egorin MJ (2005) Pharmacokinetics and pharmacodynamics of 17-demethoxy 17-[[(2-dimethylamino)ethyl]amino]geldanamycin (17DMAG, NSC 707545) in C.B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts. Cancer Chemother Pharmacol 55:21–32PubMedGoogle Scholar
  33. Engstrom WE, Barrios C, Azawedo E, Mollermark G, Kangstrom LE, Eliason I, Larsson O (1987) Expression of c-myc in canine mammary tumours. Anticancer Res 1:1235–1238Google Scholar
  34. Enmon R, Yang WH, Ballangrud AM, Solit DB, Heller G, Rosen N, Scher HI, Sgouros G (2003) Combination treatment with 17-N-allylamino-17-demethoxy geldanamycin and acute irradiation produces supra-additive growth suppression in human prostate carcinoma spheroids. Cancer Res 63:8393–8399PubMedGoogle Scholar
  35. Gabai VL, Budagova KR, Sherman MY (2005) Increased expression of the major heat shock protein Hsp72 in human prostate carcinoma cells is dispensable for their viability but confers resistance to a variety of anticancer agents. Oncogene 24:3328–3338PubMedGoogle Scholar
  36. Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G (2006) Heat shock proteins 27 and 70. Anti-apoptotic proteins with tumorigenic properties. Cell Cycle 5:2592–2601PubMedGoogle Scholar
  37. George P, Bali P, Cohen P et al (2004) Cotreatment with 17-allylamino-demethoxygeldanamycin and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3. Cancer Res 64:3645–3652PubMedGoogle Scholar
  38. George P, Bali P, Annavarapu S et al (2005) Combination of the histone deacetylase inhibitor LBH589 and the Hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood 105:1768–1776PubMedGoogle Scholar
  39. Gibbons NB, Watson RWG, Coffey RNT, Brady HP, Fitzpatrick JM (2000) Heat-shock proteins inhibit induction of prostate cancer cell apoptosis. Prostate 45:58–65PubMedGoogle Scholar
  40. Glaze ER, Lambert AL, Smith AC et al (2005) Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance. Cancer Chemother Pharmacol 56:637–647PubMedGoogle Scholar
  41. Goetz MP, Toft D, Reid J et al (2005) Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer. J Clin Oncol 23:1078–1087PubMedGoogle Scholar
  42. Grem JL, Morrison G, Guo XD et al (2005) Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors. J Clin Oncol 23:1885–1893PubMedGoogle Scholar
  43. Guo F, Rocha K, Bali P et al (2005) Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin. Cancer Res 65:10536–10544PubMedGoogle Scholar
  44. Hansen RK, Parra I, Lemieux P, Oesterreich S, Hilsenbeck SG, Fuqua SA (1999) Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells. Breast Cancer Res Treat 56:187–196PubMedGoogle Scholar
  45. Hansen RK, Parra I, Hilsenbeck SG, Himelstein B, Fuqua SAW (2001) Hsp27-induced MMp-9 expression is influenced by the Src tyrosine protein kinase Yes. Biochem Biophys Res Commun 282:186–193PubMedGoogle Scholar
  46. He LF, Guan KP, Yan Z, Ye HY, Xu KX, Ren L, Hou SK (2005) Enhanced sensitivity to mitomycin C by abating heat shock protein 70 expression in human bladder cancer cell line of BIU-87. Chin Med J 118:1965–1972PubMedGoogle Scholar
  47. Hell-Pourmojib M, Neuner P, Fischer H, Rezaie S, Kindås-Mügge I, Knobler R, Trautinger F (2002) Differential expression of a novel gene in response to Hsp27 and cell differentiation in human keratinocytes. J Invest Dermatol 119:154–159PubMedGoogle Scholar
  48. Helmbrecht K, Zeise E, Reinsing L (2000) Chaperones in cell cycle regulation and mitogenic signal transduction: a review. Cell Prolif 33:341–365PubMedGoogle Scholar
  49. Hollingshead M, Alley M, Burger AM, Borgel S, Pacula-Cox C, Fiebig HH, Sausville EA (2005) In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative. Cancer Chemother Pharmacol 56:115–125PubMedGoogle Scholar
  50. Hurlimann J, Gebhard S, Gomez F (1993) Oestrogen receptor, progesterone receptor, pS2, Erd5, Hsp27 and cathepsin D in invasive ductal breast carcinomas. Histopathology 23:239–248PubMedGoogle Scholar
  51. Ioachim E, Tsanou E, Briasoulis E, Batsis Ch, Karavasilis V, Charchanti A, Pavlidis N, Agnantis NJ (2003) Clinicopathological study of the expression of hsp27, pS2, cathepsin D and metallothionein in primary invasive breast cancer. Breast 12:111–1119PubMedGoogle Scholar
  52. Jameel A, Skilton RA, Campbell TA, Chander SK, Coombes RC, Luqmani YA (1992) Clinical and biological significance of Hsp89 alpha in human breast cancer. Int J Cancer 50:409–415PubMedGoogle Scholar
  53. Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92:1564–1572PubMedGoogle Scholar
  54. Jonak C, Klosner G, Kokesch C, Födinger D, Hönigsmann H, Trautinger F (2002) Subcorneal colocalization of the small heat shock protein, Hsp27, with keratins and proteins of the cornified cell envelope. Br J Dermatol 147:13–19PubMedGoogle Scholar
  55. Jones EL, Zhao MJ, Stevenson MA, Calderwood SK (2004) The 70 kilodalton heat shock protein is an inhibitor of apoptosis in prostate cancer. Int J Hyperthermia 20:835–849PubMedGoogle Scholar
  56. Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, Burrows FJ (2003) A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425:407–410PubMedGoogle Scholar
  57. Kano R, Abe K, Hasegawa A (2004) cDNA of canine heat shock protein 70 (HSP70). Vet Res Commun 28:395–405PubMedGoogle Scholar
  58. Kaur J, Srivastava A, Ralhan R (1998) Expression of 70-kDa heat shock protein in oral lesions: marker of biological stress or pathogenicity. Oral Oncol 34:496–501PubMedGoogle Scholar
  59. Kaur J, Kaur J, Ralhan R (2000) Induction of apoptosis by abrogation of HSP70 expression in human oral cancer cells. Int J Cancer 85:1–5PubMedGoogle Scholar
  60. Kaur G, Belotto D, Burger AM et al (2004) Antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: an orally bioavailable heat shock protein 90 modulator. Clin Cancer Res 10:4813–4821PubMedGoogle Scholar
  61. Kiriyama MT, Oka M, Takehana M, Kobayashi S (2001) Expression of a small heat shock protein 27 (Hsp27) in mouse skin tumors induced by UVB-irradiation. Biol Pharm Bull 24:197–200PubMedGoogle Scholar
  62. Kirkness EF, Bafna V, Halpern AL et al (2003) The dog genome: survey sequencing and comparative analysis. Science 301:1898–1903PubMedGoogle Scholar
  63. Korneeva I, Bongiovanni AM, Girotra M, Caputo TA, Witkin SS (2000) Serum antibodies to the 27-kd heat shock protein in women with gynecologic cancers. Am J Obstet Gynecol 183:18–21PubMedGoogle Scholar
  64. Kumar S, Walia V, Ray M, Elble RC (2007) p53 in breast cancer: mutation and countermeasures. Front Biosci 12:4168–4178PubMedGoogle Scholar
  65. Kumaraguruparan R, Karunagaran D, Balachandran C, Murali Manohar B, Nagini S (2006) Of human and canines: a comparative evaluation of heat shock and apoptosis-associated proteins in mammary tumours. Clin Chim Acta 365:168–176PubMedGoogle Scholar
  66. Lange BMH, Bachi A, Wilm M, Gonzales C (2000) Hsp90 is a core centrosomal component and is required at different stages of the centrosome cycle in Drosophila and vertebrates. EMBO J 19:1252–1262PubMedGoogle Scholar
  67. Larsen JK, Gerthoffer WT, Hickey E, Weber LA (1995) Cloning and sequencing of a cDNA encoding the canine Hsp27 protein. Gene 161:305–306PubMedGoogle Scholar
  68. Lattouf JB, Srinivasan R, Pinto PA, Linehan WM, Neckers L (2006) Mechanisms of disease: the role of heat-shock protein 90 in genitourinary malignancy. Nat Clin Pract Urol 3:590–601PubMedGoogle Scholar
  69. Lazaris AC, Chatzigianni EB, Panoussopoulos D, Tzimas GN, Davaris PS, Golematis BC (1997) Proliferating cell nuclear antigen and heat shock protein 70 immunolocalization in invasive ductal breast cancer not otherwise specified. Breast Cancer Res Treat 43:43–51PubMedGoogle Scholar
  70. Lemieux P, Oesterreich S, Lawrence JA, Steeg PS, Hilsenbeck SG, Harvey JM, Fuqua SAW (1997) The small heat shock protein Hsp27 increases invasiveness but decreases motility of breast cancer cells. Invasion Metastasis 17:113–123PubMedGoogle Scholar
  71. Li Z (2001) The roles of heat shock proteins in tumour immunity. In: Giaccone G, Schilsky R, Sondel P (eds) Cancer chemotherapy and biological response modifiers. Elsevier, New York, pp 371–382Google Scholar
  72. Love S, King RJB (1994) A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer. Br J Cancer 69:743–748PubMedGoogle Scholar
  73. Luo LY, Herrera I, Soosaipillai A, Diamandis EP (2002) Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library. Br J Cancer 87:339–343PubMedGoogle Scholar
  74. Machida H, Nakajima S, Shikano N, Nishio J, Okada S, Asayama M, Shirai M, Kubota N (2005) Heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin potentiates the radiation response of tumor cells grown as monolayer cultures and spheroids by inducing apoptosis. Cancer Sci 96:911–917PubMedGoogle Scholar
  75. Martin de las Mulas J, Ordas J, Millan Y, Fernandez-Soria V, Ramon y Cajal S (2003) Oncogene HER-2 in canine mammary gland carcinomas: an immunohistochemical and chromogenic in situ hybridization study. Breast Cancer Res Treat 80:363–367PubMedGoogle Scholar
  76. Mathew A, Morimoto RI (1998) Role of the heat-shock response in the life and death of protein. Ann N Y Acad Sci 851:99–111PubMedGoogle Scholar
  77. Matsuyama S, Nakamura M, Yonezawa K, Shimada T, Ohashi F, Takamori Y, Kubo K (2001) Expression patterns of the erbB subfamily mRNA in canine benign and malignant mammary tumors. J Vet Med Sci 63:949–954PubMedGoogle Scholar
  78. McCollum AK, Teneyck CJ, Sauer BM, Toft DO, Erlichman C (2006) Up-regulation of heat shock protein 27 induces resistance to 17-allylamino-demethoxygeldanamycin through a glutathione-mediated mechanism. Cancer Res 66:10967–10975PubMedGoogle Scholar
  79. Mesa RA, Loegering D, Powell HL et al (2005) Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine. Blood 106:318–327PubMedGoogle Scholar
  80. Milarski KL, Morimoto RI (1986) Expression of human Hsp70 during the synthetic phase of the cell cycle. Proc Natl Acad Sci U S A 83:9517–9521PubMedGoogle Scholar
  81. Misdorp W (2002) Tumors of the mammary gland. In: Meuten DJ (ed) Tumors in domestic animals. Iowa State, Ames, IA, pp 575–606Google Scholar
  82. Miyata Y (2005) Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents. Curr Pharm Des 11:1131–1138PubMedGoogle Scholar
  83. Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–3796PubMedGoogle Scholar
  84. Mosser DD, Morimoto RI (2004) Molecular chaperones and the stress of oncogenesis. Oncogene 23:2907–2918PubMedGoogle Scholar
  85. Mueller F, Fuchs B, Kaser-Hotz B (2007) Comparative biology of human and canine osteosarcoma. Anticancer Res 27:155–164PubMedGoogle Scholar
  86. Multhoff G (2006) Heat shock proteins in immunity. Handb Exp Pharmacol 172:279–304PubMedGoogle Scholar
  87. Neckers L (2006) Chaperoning oncogenes: Hsp90 as a target of geldanamycin. Handb Exp Pharmacol 172:259–277PubMedGoogle Scholar
  88. Nguyen DM, Lorang D, Chen GA, Stewart JH 4th, Tabibi E, Schrump DS (2001) Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis. Ann Thorac Surg 72:371–379PubMedGoogle Scholar
  89. Nollen EAA, Morimoto RI (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins. J Cell Sci 115:2809–2816PubMedGoogle Scholar
  90. Nowakowski GS, McCollum AK, Ames MM et al (2006) A phase I trial of twice-weekly 17-allylamino-demethoxy-geldanamycin in patients with advanced cancer. Clin Cancer Res 12:6087–6093PubMedGoogle Scholar
  91. Nylandsted J, Rohde M, Brand K, Bastholm L, Elling F, Jäättelä M (2000) 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 U S A 97:7871–7876PubMedGoogle Scholar
  92. Nylandsted J, Wick W, Hirt UA, Brand K, Rohde M, Leist M, Weller M, Jäättelä M (2002) Eradication of glioblastoma and breast and colon carcinoma xenografts by Hsp70 depletion. Cancer Res 62:7139–7142PubMedGoogle Scholar
  93. Oesterreich S, Weng CN, Qiu M, Hilsenbeck SG, Osborne CK, Fuqua SA (1993) The small heat shock protein hsp27 is correlated with growth and drug resistance in human breast cancer cell lines. Cancer Res 53:4443–4448PubMedGoogle Scholar
  94. Oesterreich S, Hilsenbeck SG, Ciocca DR, Allred DC, Clark GM, Chamness GC, Osborne CK, Fuqua SAW (1996) The small heat shock protein Hsp27 is not an independent prognostic marker in axillary lymph node-negative breast cancer patients. Clin Cancer Res 2:1199–1206PubMedGoogle Scholar
  95. Oka M, Sato S, Soda H et al (2001) Autoantibody to heat shock protein Hsp40 in sera of lung cancer patients. Jpn J Cancer Res 92:316–320PubMedGoogle Scholar
  96. O’Neill PA, Shaaban AM, West CR et al (2004) Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27. Br J Cancer 90:182–188PubMedGoogle Scholar
  97. Pearl LH (2005) Hsp90 and Cdc37—a chaperone cancer conspiracy. Curr Opin Genet Dev 15:55–61PubMedGoogle Scholar
  98. Peng Y, Chen L, Li C, Lu W, Chen J (2001) Inhibition of MDM2 by Hsp90 contributes to mutant p53 stabilization. J Biol Chem 276:40583–40590PubMedGoogle Scholar
  99. Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL, Kluger HM (2007) High Hsp90 expression is associated with decreased survival in breast cancer. Cancer Res 67:2932–2937PubMedGoogle Scholar
  100. Pinder SE, Balsitis M, Ellis IO, Landon M, Mayer RJ, Lowe J (1994) The expression of alpha B-crystallin in epithelial tumours: a useful tumour marker? J Pathol 174:209–215PubMedGoogle Scholar
  101. Plescia J, Salz W, Xia F et al (2005) Rational design of shepherdin, a novel anticancer agent. Cancer Cell 7:457–468PubMedGoogle Scholar
  102. Pratt WB, Toft DO (1997) Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18:306–360PubMedGoogle Scholar
  103. Premkumar DR, Arnold B, Pollack IF (2006) Cooperative inhibitory effect of ZD1839 (Iressa) in combination with 17-AAG on glioma cell growth. Mol Carcinog 45:288–301PubMedGoogle Scholar
  104. Price JT, Quinn JM, Sims NA et al (2005) The heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamicin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line. Cancer Res 65:4929–4934PubMedGoogle Scholar
  105. Rahmani M, Yu C, Dai Y, Reese E, Ahmed W, Dent P, Grant S (2003) Coadministration of the heat shock protein 90 antagonist 17-allylamino-17-demethoxygeldanamycin with suberoylanilide hydroxamic acid or sodium butyrate synergistically induces apoptosis in human leukemia cells. Cancer Res 63:8420–8427PubMedGoogle Scholar
  106. Ramanathan RK, Trump DL, Eiseman JL et al (2005) Phase I pharmacokinetic-pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin (17AAG, NSC 330507), a novel inhibitor of heat shock protein 90, in patients with refractory advanced cancers. Clin Cancer Res 11:3385–3391PubMedGoogle Scholar
  107. Ritossa F (1962) A new puffing pattern induced by temperature shock and DNP in Drosophila. Experientia 18:571–573Google Scholar
  108. Robles AI, Wright MH, Gandhi B, Feis SS, Hanigan CL, Wiestner A, Varticovski L (2006) Schedule-dependent synergy between the heat shock protein 90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin and doxorubicin restores apoptosis to p53-mutant lymphoma cell lines. Clin Cancer Res 12:6547–6556PubMedGoogle Scholar
  109. Romanucci M, Bongiovanni L, Marruchella G, Marà M, Di Guardo G, Preziosi R, Della Salda L (2005) Heat shock proteins (HSPs) expression in canine intracutaneous cornifying epithelioma and squamous cell carcinoma. Vet Dermatol 16:108–116PubMedGoogle Scholar
  110. Romanucci M, Marinelli A, Sarli G, Della Salda L (2006) Heat shock proteins expression in canine malignant mammary tumours. BMC Cancer 6:171PubMedGoogle Scholar
  111. Russell JS, Burgan W, Oswald KA, Camphausen K, Tofilon PJ (2003) Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin: a multitarget approach to radiosensitization. Clin Cancer Res 9:3749–3755PubMedGoogle Scholar
  112. Rust W, Kingsley K, Petnicki T, Padmanabhan S, Carper SW, Plopper GE (1999) Heat shock protein 27 plays two distinct roles in controlling human breast cancer cell migration on laminin-5. Mol Cell Biol Res Commun 1:196–202PubMedGoogle Scholar
  113. Sain N, Krishnan B, Ormerod MG, De Rienzo A, Liu WM, Kaye SB, Workman P, Jackman AL (2006) Potentiation of paclitaxel activity by the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin in human ovarian carcinoma cell lines with high levels of activated AKT. Mol Cancer Ther 5:1197–1208PubMedGoogle Scholar
  114. Sanderson S, Valenti M, Gowan S, Patterson L, Ahmad Z, Workman P, Eccles SA (2006) Benzoquinone ansamycin heat shock protein 90 inhibitors modulate functions required for tumor angiogenesis. Mol Cancer Ther 5:522–532PubMedGoogle Scholar
  115. Schmitt E, Parcellier A, Gurbuxani S et al (2003) Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant. Cancer Res 63:8233–8240PubMedGoogle Scholar
  116. Schmitt E, Maingret L, Puig PE et al (2006) Heat shock protein 70 neutralization exerts potent antitumor effects in animal models of colon cancer and melanoma. Cancer Res 66:4191–4197PubMedGoogle Scholar
  117. Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C (2007) Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol 81:15–27PubMedGoogle Scholar
  118. Shadad FN, Ramanathan RH (2006) 17-dimethylaminoethylamino-17-demethoxygeldanamycin in patients with advanced-stage solid tumors and lymphoma: a phase I study. Clin Lymphoma Myeloma 6:500–501PubMedCrossRefGoogle Scholar
  119. Sharp S, Workman P (2006) Inhibitors of the Hsp90 molecular chaperone: current status. Adv Cancer Res 95:323–348PubMedGoogle Scholar
  120. Shi Y, Thomas JO (1992) The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate. Mol Cell Biol 12:2186–2192PubMedGoogle Scholar
  121. Shin KD, Lee M, Shin D et al (2005) Blocking tumor cell migration and invasion with biphenyl isoxazole derivative KRIBB3, a synthetic molecule that inhibits Hsp27 phosphorylation. J Biol Chem 280:41439–41448PubMedGoogle Scholar
  122. Shintani S, Zhang T, Aslam A, Sebastian K, Yoshimura T, Hamakawa H (2006) P53-dependent radiosensitizing effects of Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin on human oral squamous cell carcinoma cell lines. Int J Oncol 29:1111–1117PubMedGoogle Scholar
  123. Shyamala G, Schweitzer M, Ullrich SJ (1993) Relationship between 90-kilodalton heat shock protein, estrogen receptor, and progesterone receptor in human mammary tumors. Breast Cancer Res Treat 26:95–100PubMedGoogle Scholar
  124. Smith V, Sausville EA, Camalier RF, Fiebig HH, Burger AM (2005) Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: effects on Hsp90 and client proteins in melanoma models. Cancer Chemother Pharmacol 56:126–137PubMedGoogle Scholar
  125. Solit DB, Basso AD, Olshen AB, Scher HI, Rosen N (2003) Inhibition of heat shock proteins 90 function down-regulates Akt kinase and sensitizes tumors to taxol. Cancer Res 63:2139–2144PubMedGoogle Scholar
  126. Sutter NB, Ostrander EA (2004) Dog star rising: the canine genetic system. Nat Rev Genet 5:900–910PubMedGoogle Scholar
  127. Switonski M, Szczerbal I, Nowacka J (2004) The dog genome map and its use in mammalian comparative genomics. J Appl Genet 45:195–214PubMedGoogle Scholar
  128. Sydor JR, Normant E, Pien CS et al (2006) Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90. Proc Natl Acad Sci U S A 103:17408–17413PubMedGoogle Scholar
  129. Takahashi S, Mikami T, Watanabe Y et al (1994) Correlation of heat shock protein 70 expression with estrogen receptor levels in invasive human breast cancer. Am J Clin Pathol 101:519–525PubMedGoogle Scholar
  130. Takahashi S, Narimatsu E, Asanuma H et al (1995) Immunohistochemical detection of estrogen receptor in invasive human breast cancer: correlation with heat shock proteins, pS2 and oncogene products. Oncology 52:371–375PubMedCrossRefGoogle Scholar
  131. Talmadge JE, Singh RK, Fidler IJ, Raz A (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170:793–804PubMedGoogle Scholar
  132. Têtu B, Brisson J, Landry J, Huot J (1995) Prognostic significance of heat-shock protein-27 in node-positve breast carcinoma: an immunohistochemical study. Breast Cancer Res Treat 36:93–97PubMedGoogle Scholar
  133. Thanner F, Sutterlin MW, Kapp M, Rieger L, Kristen P, Dietl J, Gassel AM, Muller T (2003) Heat-shock protein 70 as a prognostic marker in node-negative breast cancer. Anticancer Res 23:1057–1062PubMedGoogle Scholar
  134. Thanner F, Sutterlin MW, Kapp M et al (2005) Heat shock protein 27 is associated with decreased survival in node-negative breast cancer patients. Anticancer Res 25:1649–1653PubMedGoogle Scholar
  135. Thor A, Benz C, Moore D et al (1991) Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations. J Natl Cancer Inst 83:170–178PubMedGoogle Scholar
  136. Tissieres A, Mitchell HK, Tracy UM (1974) Protein synthesis in salivary glands of Drosophila melanogaster. Relation to chromosome puffs. J Mol Biol 84:389–398PubMedGoogle Scholar
  137. Trautinger F, Kindas-Mugge I, Dekrout B, Knobler RM, Metze D (1995) Expression of the 27-kDa heat shock protein in human epidermis and in epidermal neoplasms: an immunohistochemical study. Br J Dermatol 133:194–200PubMedGoogle Scholar
  138. Trieb K, Gerth R, Windhager R, Grohs JG, Holzer G, Berger P, Kotz R (2000) Serum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma. Immunobiology 201:368–376PubMedGoogle Scholar
  139. Tsutsumi-Ishii Y, Tadokoro K, Hanaoka F, Tsuchida N (1995) Response of heat shock element within the human hsp70 promoter to mutated p53 genes. Cell Growth Differ 6:1–8PubMedGoogle Scholar
  140. Vail DM, MacEwen EG (2000) Spontaneously occurring tumors of companion animals as models for human cancer. Cancer Investig 18:781–792Google Scholar
  141. Van Leeuwen IS, Hellmén E, Cornelisse CJ, Van der Burg B, Rutteman GR (1996) p53 mutations in mammary tumor cell lines and corresponding tumor tissues in the dog. Anticancer Res 16:3737–3743PubMedGoogle Scholar
  142. Vargas-Roig LM, Fanelli MA, Lopez LA, Gago FE, Tello O, Aznar JC, Ciocca DR (1997) Heat shock proteins and cell proliferation in human breast cancer biopsy samples. Cancer Detect Prev 21:441–451PubMedGoogle Scholar
  143. Vasilevskaya IA, O’Dwyer PJ (2005) 17-Allylamino-17-demethoxygeldanamycin overcomes TRAIL resistance in colon cancer cell lines. Biochem Pharmacol 70:580–589PubMedGoogle Scholar
  144. Whitesell L, Lindquist SL (2005) Hsp90 and the chaperoning of cancer. Nat Rev Cancer 5:761–772PubMedGoogle Scholar
  145. Whitley D, Goldberg SP, Jordan WD (1999) Heat shock proteins: a review of the molecular chaperones. J Vasc Surg 29:748–751PubMedGoogle Scholar
  146. Xiao L, Lu X, Ruden DM (2006) Effectiveness of Hsp90 inhibitors as anti-cancer drugs. Mini Rev Med Chem 6:1137–1143PubMedGoogle Scholar
  147. Xu W, Mimnaugh E, Rosser MFN, Nicchitta C, Marcu M, Yarden Y, Neckers L (2001) Sensitivity of mature ErbB2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90. J Biol Chem 276:3702–3708PubMedGoogle Scholar
  148. Yano M, Naito Z, Yokoyama M, Shiraki Y, Ishiwata T, Inokuchi M, Asano G (1999) Expression of Hsp90 and Cyclin D1 in human breast cancer. Cancer Lett 137:45–51PubMedGoogle Scholar
  149. Yao Q, Nishiuchi R, Kitamura T, Kersey JH (2005) Human leukemias with mutated FLT3 kinase are synergistically sensitive to FLT3 and Hsp90 inhibitors: the key role of the STAT5 signal transduction pathway. Leukemia 19:1605–1612PubMedGoogle Scholar
  150. Zeise E, Kuhl N, Kunz J, Rensing L (1998) Nuclear translocation of stress protein Hsc70 during S phase in rat C6 glioma cells. Cell Stress Chaperones 3:94–99PubMedGoogle Scholar
  151. Zhao Z, Shen W (2005) Heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901. World J Gastroenterol 11:73–78PubMedGoogle Scholar
  152. Zhong L, Peng X, Hidalgo GE, Doherty DE, Stromberg AJ, Hirschowitz EA (2003) Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients. Cancer Detect Prev 27:285–290PubMedGoogle Scholar

Copyright information

© Cell Stress Society International 2008

Authors and Affiliations

  • Mariarita Romanucci
    • 1
  • Tania Bastow
    • 1
  • Leonardo Della Salda
    • 1
    Email author
  1. 1.Department of Comparative Biomedical Sciences, Faculty of Veterinary MedicineUniversity of TeramoTeramoItaly

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