Heat-shock-protein-27(HSP27) expression in ovarian carcinoma: Relation in response to chemotherapy and prognosis

Arts, Henriëtte J.G.; Hollema, Harry; Lemstra, Willy; Willemse, Pax H.B.; Vries, Elisabeth G.E. de; Kampinga, Harm H.; Zee, Ate G.J. van der

doi:10.1002/(sici)1097-0215(19990621)84:3<234::aid-ijc6>3.0.co;2-9

Cited by 110 publications

(96 citation statements)

References 13 publications

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“…For example, overexpression of hsp27 has been found to cause resistance to Adriamycin in breast cancer cells (37) by increasing efficiency in repair of Adriamycin-induced DNA damages (38). Overexpression of hsp27 has been thought to cause drug resistance and poor prognosis in breast (39) and ovarian (40,41) cancers.…”

Section: Discussionmentioning

confidence: 99%

Identification of 14-3-3σ as a Contributor to Drug Resistance in Human Breast Cancer Cells Using Functional Proteomic Analysis

et al. 2006

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Multidrug resistance (MDR) is a major obstacle to successful cancer treatment. To understand the mechanism of MDR, many cancer cell lines have been established, and various mechanisms of resistance, such as ATP-binding cassette (ABC) transporter-mediated drug efflux, have been discovered. Previously, a MDR cell line MCF7/AdVp3000 was selected from breast cancer cell line MCF7 against Adriamycin, and overexpression of ABCG2 was thought to cause MDR in this derivative cell line. However, ectopic overexpression of ABCG2 in MCF7 cells could not explain the extremely high drug resistance level of the selected MCF7/AdVp3000 cells. We hypothesized that MCF7/AdVp3000 cells must have other resistance mechanisms selected by Adriamycin. To test this hypothesis, we compared the global protein profiles between MCF7 and MCF7/AdVp3000 cells. Following two-dimensional gel electrophoresis and matrix-assisted laser desorption/ ionization-time of flight mass spectrometry analysis, 17 protein spots with differential levels between the two cell lines were identified. Although 14-3-3S, keratin 18, keratin 19, ATP synthase B, protein disulfide isomerase, heat shock protein 27, cathepsin D, triose-phosphate isomerase, peroxiredoxin 6, and electron transfer flavoprotein were increased, nm23/H1, peroxiredoxin 2, nucleophosmin 1/B23, and inorganic pyrophosphatase were decreased in MCF7/AdVp3000 cells. The differential levels of these proteins were validated using Western blot. Furthermore, functional validation showed that the elevated 14-3-3S expression contributes considerably to the observed drug resistance in MCF7/AdVp3000 cells. We, thus, conclude that these proteins likely contribute to the resistance selected in the MCF7/AdVp3000 cells, and their altered expression in tumors may cause clinical resistance to chemotherapy. (Cancer Res 2006; 66(6): 3248-55)

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Section: Discussionmentioning

confidence: 99%

Identification of 14-3-3σ as a Contributor to Drug Resistance in Human Breast Cancer Cells Using Functional Proteomic Analysis

et al. 2006

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“…A cDNA for HSP10 was identified by functional cloning from a retroviral cDNA library of cDNAs as seen in Table 1. Up-regulation of HSP27, HSP70, HSP72, GRP78, and HSP90 have been reported to be involved in CP-r ovarian cancer (Arts et al, 1999;Liu et al, 2002), breast cancer (Vargas-Roig et al, 1998), colon cancer (Belfi et al, 1999), cervical HeLa cells (Huang et al, 2000), and laryngeal carcinoma cells (Brozovic et al, 2001). However, overexpression of ERp29, which up-regulates Hsp27 in breast cancer cells, increases resistance to doxorubicin, but not cisplatin or paclitaxel (Zhang and Putti, 2010).…”

Section: A Heat Shock Proteinsmentioning

confidence: 99%

Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes

et al. 2012

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“…Various roles have been proposed for Hsp27 to explain its cytoprotective effects during cellular stress, including its role as a molecular chaperone, inhibitor of protein unfolding, direct interference with caspase activation, modulation of oxidative stress, and regulation of the cytoskeleton (9). Higher levels of Hsp27 are commonly detected in various cancers including breast (10), gastric (11), ovarian and endometrial (12,13), osteosarcoma (14), glial tumors (15), and prostate (16). Increased Hsp27 levels in breast, endometrial, and gastric cancer is associated with metastasis, poor prognosis, and resistance to chemotherapy or radiation (10,(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Increased Hsp27 after Androgen Ablation Facilitates Androgen-Independent Progression in Prostate Cancer via Signal Transducers and Activators of Transcription 3–Mediated Suppression of Apoptosis

et al. 2005

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One strategy to improve therapies in prostate cancer involves targeting cytoprotective genes activated by androgen withdrawal to delay the emergence of the androgen-independent (AI) phenotype. The objectives of this study were to define changes in Hsp27 levels after androgen ablation and to evaluate the functional relevance of these changes in AI progression. Using a tissue microarray of 232 specimens of hormone-naïve and post-hormone ablation-treated prostate cancer, we found that Hsp27 levels increase after androgen ablation to become highly expressed (>4-fold, P V 0.01) in AI tumors. Hsp27 overexpression rendered LNCaP cells highly resistant to androgen withdrawal both in vitro and in vivo. Tumor volume and serum prostate-specific antigen levels increased 4.3-and 10-fold faster after castration when Hsp27 was overexpressed. Treatment of LNCaP tumor cells in vitro with Hsp27 antisense oligonucleotides (ASO) or shortinterfering RNA suppressed Hsp27 levels in a dose-dependent and sequence-specific manner increased the apoptotic sub-G 0 -G 1 fraction and caspase-3 cleavage >2-fold, as well as decreased signal transducers and activators of transcription 3 (Stat3) levels and its downstream genes, c-fos and sPLA-2. The cytoprotection afforded by Hsp27 overexpression was attenuated by Stat3 knockdown using specific Stat3 ASO. Coimmunoprecipitation and immunofluorescence confirmed that Hsp27 interacts with Stat3 and that Stat3 levels correlated directly with Hsp27 levels. Hsp27 ASO treatment in athymic mice bearing LNCaP tumors significantly delayed LNCaP tumor growth after castration, decreasing mean tumor volume and serum prostate-specific antigen levels by 57% and 69%, respectively. These findings identify Hsp27 as a modulator of Stat3-regulated apoptosis after androgen ablation and as a potential therapeutic target in advanced prostate cancer. (Cancer Res 2005; 65(23): 11083-93)

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Heat-shock-protein-27(HSP27) expression in ovarian carcinoma: Relation in response to chemotherapy and prognosis

Cited by 110 publications

References 13 publications

Identification of 14-3-3σ as a Contributor to Drug Resistance in Human Breast Cancer Cells Using Functional Proteomic Analysis

Identification of 14-3-3σ as a Contributor to Drug Resistance in Human Breast Cancer Cells Using Functional Proteomic Analysis

Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes

Increased Hsp27 after Androgen Ablation Facilitates Androgen-Independent Progression in Prostate Cancer via Signal Transducers and Activators of Transcription 3–Mediated Suppression of Apoptosis

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