Heat shock protein 27 increases after androgen ablation and plays a cytoprotective role in hormone-refractory prostate cancer

Cancer Research
Palma RocchiMartin E Gleave

Abstract

Heat shock protein 27 (Hsp27) is a chaperone implicated as an independent predictor of clinical outcome in prostate cancer. Our aim was to characterize changes in Hsp27 after androgen withdrawal and during androgen-independent progression in prostate xenografts and human prostate cancer to assess the functional significance of these changes using antisense inhibition of Hsp27. A tissue microarray was used to measure changes in Hsp27 protein expression in 232 specimens from hormone naive and posthormone-treated cancers. Hsp27 expression was low or absent in untreated human prostate cancers but increased beginning 4 weeks after androgen-ablation to become uniformly highly expressed in androgen-independent tumors. Androgen-independent human prostate cancer PC-3 cells express higher levels of Hsp27 mRNA in vitro and in vivo, compared with androgen-sensitive LNCaP cells. Phosphorothioate Hsp27 antisense oligonucleotides (ASOs) and small interference RNA potently inhibit Hsp27 expression, with increased caspase-3 cleavage and PC3 cell apoptosis and 87% decreased PC3 cell growth. Hsp27 ASO and small interference RNA also enhanced paclitaxel chemosensitivity in vitro, whereas in vivo, systemic administration of Hsp27 ASO in athymic mic...Continue Reading

References

Jun 6, 1991·Nature·A J LevineC A Finlay
Apr 1, 1990·Immunology Today·S H Kaufmann
Jan 1, 1986·The Prostate·M L MontpetitM Tenniswood
Oct 6, 1993·Journal of the National Cancer Institute·D R CioccaS A Fuqua
Feb 25, 1996·Experimental Cell Research·A Samali, T G Cotter
Feb 14, 1998·Nature Medicine·B JansenH Pehamberger
Oct 7, 1998·International Journal of Cancer. Journal International Du Cancer·L M Vargas-RoigD R Ciocca
Oct 21, 1999·Journal of the National Cancer Institute·L BubendorfO P Kallioniemi
Aug 29, 2000·The Prostate·N B GibbonsJ M Fitzpatrick
Mar 20, 2002·Nature Reviews. Cancer·B J Feldman, D Feldman
Jan 3, 2003·Apoptosis : an International Journal on Programmed Cell Death·C G ConcannonA Samali
Jun 25, 2003·Expert Review of Anticancer Therapy·Tomasz M BeerKristine M Eilers
Jan 2, 2004·Nature Medicine·Charlie D ChenCharles L Sawyers

❮ Previous
Next ❯

Citations

Mar 21, 2007·Der Urologe. Ausg. A·B A HadaschikM E Gleave
Mar 17, 2005·World Journal of Urology·Alan SoColleen Nelson
Dec 1, 2006·Apoptosis : an International Journal on Programmed Cell Death·Szabolcs BellyeiFerenc Gallyas
Feb 20, 2009·Pharmaceutical Research·Mark P BorgmanHamidreza Ghandehari
May 12, 2005·Urology·Matthew R Smith, Joel B Nelson
Sep 12, 2009·Molecular Pharmaceutics·Mark P BorgmanHamidreza Ghandehari
May 14, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elie HadchityClaire Rodriguez-Lafrasse
Aug 16, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Virginie BaylotPalma Rocchi
Nov 8, 2006·Nature Clinical Practice. Urology·Jean-Baptiste LattoufLeonard Neckers
May 21, 2005·Nature Reviews. Cancer·Martin E Gleave, Brett P Monia
Nov 21, 2012·Prostate Cancer and Prostatic Diseases·N VasiljevićA T Lorincz
May 31, 2006·Molecular & Cellular Proteomics : MCP·Carlos A CasianoEng M Tan
Jan 23, 2013·The Cancer Journal·Robert R ZielinskiKim N Chi
Jan 30, 2007·Journal of Clinical Pathology·Ashish B RajputDavid G Huntsman
Feb 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amina ZoubeidiMartin Gleave
Jul 26, 2005·Cell Stress & Chaperones·Daniel R Ciocca, Stuart K Calderwood
May 14, 2011·Endocrine-related Cancer·Kate L MahonLisa G Horvath
Dec 15, 2010·Future Oncology·Anthony KoupparisMartin E Gleave
May 11, 2012·Future Medicinal Chemistry·Z NahlehZ Nahle
Sep 26, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·M ZhaoQ Chen
Mar 19, 2013·Journal of Proteomics·Ioannis P TrougakosVassilis G Gorgoulis
Apr 10, 2014·Asian Journal of Andrology·Costantine Albany, Noah M Hahn
Aug 1, 2012·Journal of Cancer Research and Clinical Oncology·Bin ZhangXue-Ping Feng
Jul 13, 2006·Expert Review of Anticancer Therapy·Nancy A Dawson
Jul 8, 2005·Expert Review of Proteomics·Till BraunschweigStephen M Hewitt
Apr 26, 2006·Expert Opinion on Investigational Drugs·Hideaki MiyakeMartin E Gleave
Nov 28, 2013·Expert Opinion on Emerging Drugs·Paul H ChungGanesh V Raj
May 1, 2007·FEBS Letters·André-Patrick ArrigoPatrick Vicart
Jan 26, 2016·International Journal of Molecular Sciences·Mitsuru OkunoIchiro Yasuda
Feb 12, 2013·Molecular and Cellular Endocrinology·Laia Querol CanoCharlotte L Bevan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis