Detection and distribution of heat shock proteins 27 and 90 in human benign and malignant prostatic tissue

Thomas, Siep; Brown, Ian; Hollins, Graham; Hocken, A G; Kirk, D.; King, R. J. B.; Leake, R E

doi:10.1046/j.1464-410x.1996.09058.x

Cited by 33 publications

(23 citation statements)

References 5 publications

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“…The cytoprotective effects of Hsp27 may result from its role as molecular chaperone or through direct interference with caspase activation, modulation of oxidative stress, and regulation of the cytoskeleton (45,46). Several previous studies identify Hsp27 as an independent survival factor in prostate cancer (28,47,48). The aims of this study were to characterize the changes in Hsp27 expression after androgen withdrawal and during androgen-independent progression and to assess its functional significance role in hormone-refractory prostate cancer using ASO or siRNA loss-of-function analyses.…”

Section: Discussionmentioning

confidence: 98%

Heat Shock Protein 27 Increases after Androgen Ablation and Plays a Cytoprotective Role in Hormone-Refractory Prostate Cancer

et al. 2004

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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 mice decreased PC-3 tumor progression and also significantly enhanced paclitaxel chemosensitivity. These findings suggest that increased levels of Hsp27 after androgen withdrawal provide a cytoprotective role during development of androgen independence and that ASO-induced silencing can enhance apoptosis and delay tumor progression.

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Section: Discussionmentioning

confidence: 98%

Heat Shock Protein 27 Increases after Androgen Ablation and Plays a Cytoprotective Role in Hormone-Refractory Prostate Cancer

et al. 2004

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“…HSP27 overexpression has been associated with prostate cancer progression and can independently predict the clinical outcome of prostate cancer, suggesting that it plays an important role in the resistance of prostate cancer to chemotherapy (Thomas et al, 1996;Cornford et al, 2000). HSP27 inhibits apoptosis by a variety of mechanisms, including sequestering cytosolic proapoptotic Cyto- chrome c, inhibiting proapoptotic tBID translocation from cytosol to the mitochondrion and preventing DAXX association with Fas receptor and subsequent JNK activation (Concannon et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells

Curtin

Cotter

2003

Br J Cancer

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Androgen-independent prostate carcinomas are resistant to chemotherapy and cell lines derived from androgen-independent prostate carcinomas such as DU 145 cells are highly resistant to Fas-mediated apoptosis. The incubation of DU 145 cells with anti-Fas IgM agonistic antibody of Fas receptor fails to activate JNK, a stress kinase involved in regulating apoptosis. We have previously shown that JNK activation is sufficient and necessary to promote Fas-mediated apoptosis in DU 145 cells. We investigate the mechanisms by which JNK activation and apoptosis are abrogated. HSP27 is overexpressed in DU 145 cells and has previously been reported to sequester DAXX and prevent JNK activation in cells treated with anti-Fas IgM. However, we find no evidence that HSP27 interacts with DAXX in DU 145 cells. Instead, we find that FADD does not interact with caspase-8 and this results in defective death-inducing signalling complex formation following Fas receptor activation.

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“…Elevated hsp27 expression has been reported in human cancer tissues and malignant cells of human origin (47)(48)(49), whereas hic-5 is markedly down-regulated in immortalized cells and cultured cell lines derived from human tumors (31,50,51). In addition, hic-5 overexpression results in development of a senescence-like phenotype in cultured cells (31,50) and increased apoptosis in cells of muscle origin (40), whereas hsp27 expression prevents apoptosis and enhances cell survival (2, 52) as well as altering cell proliferation and differentiation in a cell type-dependent manner (53)(54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of hic-5/ARA55 as an hsp27 Binding Protein

Jia¹,

Ransom²,

Shibanuma³

et al. 2001

Journal of Biological Chemistry

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hsp27 has been reported to participate in a wide variety of activities, including resistance to thermal and metabolic stress, regulation of growth and differentiation, and acting as a molecular chaperone or a regulator of actin polymerization. We hypothesized that these diverse functions are regulated in a cell-or tissue-specific manner via interaction with various binding proteins. To investigate this hypothesis, we used hsp27 as a "bait" to screen a yeast two-hybrid cDNA library from rat kidney glomeruli and identified a novel hsp27 binding protein, hic-5 (also known as ARA55), a focal adhesion protein and steroid receptor co-activator. Biochemical interaction between hsp27 and hic-5 was confirmed by co-immunoprecipitation, and critical protein⅐protein interaction regions were mapped to the hic-5 LIM domains and the hsp27 C-terminal domain. Initial analysis of the functional role of hsp27⅐hic-5 interaction revealed that hic-5 significantly inhibited the protection against heatinduced cell death conferred by hsp27 overexpression in co-transfected 293T cells. In contrast, when a non-hsp27-interacting hic-5 truncation mutant (hic-5/⌬LIM4) was co-expressed with hsp27, the hic-5 inhibition of hsp27 protection was absent. We conclude that hic-5 is a true hsp27 binding protein and inhibits the ability of hsp27 to provide protection against heat shock in an interaction-dependent manner.

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Detection and distribution of heat shock proteins 27 and 90 in human benign and malignant prostatic tissue

Abstract: The distribution of HSPs, primarily HSP 27, may aid in identifying different cell populations within prostatic carcinomas and thus help forecast biological behaviour.

Cited by 33 publications

References 5 publications

Heat Shock Protein 27 Increases after Androgen Ablation and Plays a Cytoprotective Role in Hormone-Refractory Prostate Cancer

Heat Shock Protein 27 Increases after Androgen Ablation and Plays a Cytoprotective Role in Hormone-Refractory Prostate Cancer

Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells

Identification and Characterization of hic-5/ARA55 as an hsp27 Binding Protein

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