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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 volume 24, pages 3328–3338 (2005)Cite this article

Abstract

The major heat shock protein Hsp72 is expressed at high levels in various types of cancer. Here we attempt to clarify the role of Hsp72 in prostate cancer cells by studying the effects of specific downregulation of this protein using siRNA and antisense RNA approaches. Contrary to previous reports, specific depletion of Hsp72 did not reduce viability of the prostate carcinoma cell lines PC-3 and DU-145. However, even short-term downregulation of Hsp72 in these cells made them more sensitive to hyperthermia, inhibitors of proteasome and Hsp90, and tumor necrosis factor. Interestingly, prolonged downregulation of Hsp72 in PC-3 cells over 3 weeks aggravated these effects, as well as enhanced the sensitivity of cells to oxidative stress, radiation, cis-platinum, vinblastin and taxol. The increased sensitivity to the anticancer agents was due to increased apoptosis, as well as other types of cell death, which resulted in the loss of clonogenic survival. Prolonged downregulation of Hsp72 led to severe suppression of the major survival pathways, ERK and NF-κB, which may be responsible for enhanced sensitivity of prostate carcinoma cells to a variety of anticancer treatments, as well as reduction of the cell's capability of forming colonies in soft agar.

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Abbreviations

ERK:

extracellular signal-regulated kinase

Hsp:

heat shock protein

JNK:

c-Jun N-terminal kinase

MAP:

mitogen-activated kinase

MTT:

3-[4, 5-dimethylthiasol-2-yl]-2,5-diphenyltetrasolium bromide

NF-κB:

nuclear factor kappa B

PARP:

poly(ADP-ribose) polymerase

PDB:

phorbol dibutirate

SiRNA:

small interfering RNA

TNF:

tumor necrosis factor

References

  • Adams J . (2002). Curr. Opin. Chem. Biol., 6, 493–500.

  • Adams J . (2004). Cancer Cell., 5, 417–421.

  • Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S and Elliott PJ . (1999). Cancer Res., 59, 2615–2622.

  • Ciocca DR, Clark GM, Tandon AK, Fuqua SA, Welch WJ and McGuire WL . (1993). J. Natl. Cancer Inst., 85, 570–574.

  • Costa MJM, Rosas SLB, Chindano A, Lima PDS, Madi K and Carvalho MDD . (1997). Oncol. Rep., 4, 1113–1116.

  • Dhillon AS and Kolch W . (2002). Arch. Biochem. Biophys., 404, 3–9.

  • Dhillon AS, Meikle S, Yazici Z, Eulitz M and Kolch W . (2002). EMBO J., 21, 64–71.

  • Ekedahl J, Joseph B, Marchetti P, Fauvel H, Formstecher P, Lewensohn R and Zhivotovsky B . (2003). Cancer Biol. Ther., 2, 663–669.

  • Franklin RA and McCubrey JA . (2000). Leukemia, 14, 2019–2034.

  • Gabai VL, Mabuchi K, Mosser DD and Sherman MY . (2002). Mol. Cell. Biol., 22, 3415–3424.

  • Gabai VL, Meriin AB, Mosser DD, Caron AW, Rits S, Shifrin VI and Sherman MY . (1997). J. Biol. Chem., 272, 18033–18037.

  • Gabai VL, Meriin AB, Yaglom JA, Volloch VZ and Sherman MY . (1998). FEBS Lett., 438, 1–4.

  • Gabai VL, Yaglom JA, Volloch V, Meriin AB, Force T, Koutroumanis M, Massie B, Mosser DD and Sherman MY . (2000). Mol. Cell. Biol., 20, 6826–6836.

  • Gasparian AV, Yao YJ, Kowalczyk D, Lyakh LA, Karseladze A, Slaga TJ and Budunova IV . (2002). J. Cell Sci., 115, 141–151.

  • Hanahan D and Weinberg RA . (2000). Cell, 100, 57–70.

  • Hostein I, Robertson D, DiStefano F, Workman P and Andrew Clarke P . (2001). Cancer Res., 61, 4003–4009.

  • Hunt CR, Dix DJ, Sharma GG, Pandita RK, Gupta A, Funk M and Pandita TK . (2004). Mol. Cell. Biol., 24, 899–911.

  • Hwang TS, Han HS, Choi HK, Lee YJ, Kim Y-J, Han M-Y and Park Y-M . (2003). J. Gastroenterol. Hepatol., 18, 690–700.

  • Igney FH and Krammer PH . (2002). Nat. Rev. Cancer, 2, 277–288.

  • Jaattela M . (1995). Int. J. Cancer, 60, 689–693.

  • Jaattela M . (1999). Exp. Cell Res., 248, 30–43.

  • Jaattela M, Wissing D, Kokholm K, Kallunki T and Egeblad M . (1998). EMBO J., 17, 6124–6134.

  • Jolly C and Morimoto RI . (2000). J. Natl. Cancer Inst., 92, 1564–1572.

  • Karin M and Lin A . (2002). Nat. Immunol., 3, 221–227.

  • Kucharczak J, Simmons MJ, Fan Y and Gelinas C . (2003). Oncogene, 22, 8961–8982.

  • Meriin AB, Yaglom JA, Gabai VL, Mosser DD, Zon L and Sherman MY . (1999). Mol. Cell. Biol., 19, 2547–2555.

  • Mosser DD, Caron AW, Bourget L, Denis-Larose C and Massie B . (1997). Mol. Cell. Biol., 17, 5317–5327.

  • Musch MW, Kaplan B and Chang EB . (2001). Cell Growth Differ., 12, 419–426.

  • Nanbu K, Konishi I, Mandai M, Kuroda H, Hamid AA, Komatsu T and Mori T . (1998). Cancer Detect. Prev., 22, 549–555.

  • Neckers L . (2002). Trends Mol. Med., 8, S55–S61.

  • Nylandsted J, Rohde M, Brand K, Bastholm L, Elling F and Jaattela M . (2000). Proc. Natl. Acad. Sci. USA, 97, 7871–7876.

  • Nylandsted J, Wick W, Hirt UA, Brand K, Rohde M, Leist M, Weller M and Jaattela M . (2002). Cancer Res., 62, 7139–7142.

  • Orlowski RZ, Small GW and Shi YY . (2002). J. Biol. Chem., 277, 27864–27871.

  • Papa S, Zazzeroni F, Pham CG, Bubici C and Franzoso G . (2004). J. Cell Sci., 117, 5197–5208.

  • Park H-S, Cho S-G, Kim CK, Hwang HS, Noh KT, Kim M-S, Huh S-H, Kim MJ, Ryoo K, Kim EK, Kang WJ, Lee J-S, Seo J-S, Ko Y-G, Kim S and Choi E-J . (2002). Mol. Cell. Biol., 22, 7721–7730.

  • Roninson IB . (2003). Cancer Res., 63, 2705–2715.

  • Roninson IB, Broude EV and Chang B-D . (2001). Drug Resist. Updates, 4, 303–313.

  • Seo J, Park YM, Kim JI, Shim EH, Kim CW, Jang JJ, Kim SH and Lee W . (1996). Biochem. Biophys. Res. Commun., 218, 582–587.

  • Song J, Takeda M and Morimoto RI . (2001). Nat. Cell Biol., 3, 276–282.

  • Suh J, Payvandi F, Edelstein LC, Amenta PS, Zong WX, Gelinas C and Rabson AB . (2002). Prostate, 52, 183–200.

  • Suh J and Rabson AB . (2004). J. Cell Biochem., 91, 100–117.

  • Tran SE, Holmstrom TH, Ahonen M, Kahari VM and Eriksson JE . (2001). J. Biol. Chem., 276, 16484–16490.

  • Vargasroig LM, Fanelli MA, Lopez LA, Gago FE, Tello O, Aznar JC and Ciocca DR . (1997). Cancer Detect. Prev., 21, 441–451.

  • Volloch VZ and Sherman MY . (1999). Oncogene, 18, 3648–3651.

  • Volm M, Koomagi R, Mattern J and Efferth T . (2002). Clin. Exp. Metastasis, 19, 385–390.

  • Wang CY, Cusack Jr JC, Liu R and Baldwin Jr AS . (1999). Nat. Med., 5, 412–417.

  • Wang C-Y, Mayo MW and Baldwin Jr AS . (1996). Science, 274, 784–787.

  • Wang CY, Mayo MW, Korneluk RG, Goeddel DV and Baldwin AS . (1998). Science, 281, 1680–1683.

  • Yaglom J, O'Callaghan-Sunol C, Gabai V and Sherman MY . (2003). Mol. Cell. Biol., 23, 3813–3824.

  • Yamagishi N, Miyakoshi J and Takebe H . (1997). Int. J. Radiat. Biol., 72, 157–162.

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Acknowledgements

We thank Dr Jeng-Shin Lee for retroviral plasmids and Dr D Mosser for adenoviruses. The study was supported by NIH grant (to MS), by ACS grant IRG-72-001-29 (to VG) and the International Union Against Cancer Grant (to KB).

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  1. Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, 02118, USA

    Vladimir L Gabai & Michael Y Sherman

  2. Medical Radiology Research Center, Obninsk, 249020, Russia

    Karine R Budagova

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  1. Vladimir L Gabai
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Correspondence to Michael Y Sherman.

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Gabai, V., Budagova, K. & Sherman, M. 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, 3328–3338 (2005). https://doi.org/10.1038/sj.onc.1208495

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