Heat shock protein 27 was up-regulated in cisplatin resistant human ovarian tumor cell line and associated with the cisplatin resistance

Yamamoto, Kazue; Okamoto, Aikou; Isonishi, Seiji; Ochiai, Kazunori; Ohtake, Yasuyuki

doi:10.1016/s0304-3835(01)00532-8

Cited by 75 publications

(51 citation statements)

References 19 publications

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“…The former include autophagy, an evolutionary conserved catabolic pathway that involves the sequestration and lysosomal degradation of organelles and portions of the cytoplasm (Kroemer et al, 2010), and the heat-shock response, the integrated reaction of cells to high temperatures as well as to a plethora of stressful conditions that affect protein folding (Yamamoto et al, 2001;Macleod et al, 2005;Donnelly and Blagg, 2008). Both ovarian and NSCLC cells have been shown to progressively acquire cisplatin resistance while upregulating components of the autophagic Abbreviations: CDDP, cisplatin; DYRK1B, dual-specificity Y-phosphorylation-regulated kinase 1B; EGFR, epidermal growth factor receptor; ESCC, esophageal squamous cell carcinoma; HSPs, heat-shock proteins; NSCLC, non-small cell lung cancer; PI3K, phosphoinositide-3-kinase; ROS, reactive oxygen species.…”

Section: Wang Et Al 2010mentioning

confidence: 99%

“…Presumably, this apparent discrepancy reflects the existence of multiple, sometimes cell type-specific, mechanisms that lead to cisplatin resistance. Molecular chaperones that are involved in the heatshock and unfolded protein responses, such as several heat-shock proteins, have also been shown to promote cisplatin resistance via multiple, most often indirect, mechanisms (Yamamoto et al, 2001;Zhang and Shen, 2007;Ren et al, 2008). Heat-shock protein 27 expression levels can predict the response to cisplatin-based therapies in esophageal squamous cell carcinoma patients (Miyazaki et al, 2005).…”

Section: Wang Et Al 2010mentioning

confidence: 99%

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Molecular mechanisms of cisplatin resistance

et al. 2011

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Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best known as cisplatin), are employed for the treatment of a wide array of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent (and best understood) mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis. Despite a consistent rate of initial responses, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. An intense research has been conducted during the past 30 years and several mechanisms that account for the cisplatin-resistant phenotype of tumor cells have been described. Here, we provide a systematic discussion of these mechanism by classifying them in alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre-target resistance), (2) that directly relate to DNAcisplatin adducts (on-target resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin-mediated DNA damage (post-target resistance) and (4) affecting molecular circuitries that do not present obvious links with cisplatin-elicited signals (off-target resistance). As in some clinical settings cisplatin constitutes the major therapeutic option, the development of chemosensitization strategies constitute a goal with important clinical implications.

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Section: Wang Et Al 2010mentioning

confidence: 99%

Section: Wang Et Al 2010mentioning

confidence: 99%

Molecular mechanisms of cisplatin resistance

et al. 2011

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“…Hsp-27 is also increased in >70% of patients with lymph node metastasis even when primary tumours are negative for Hsp-27 (Storm et al 1996). Hsp-27 enhances anchorage-independent growth (Rust et al 1999) and increases resistance to drugs (Ciocca et al 1992;Oesterreich et al 1993;Yamamoto et al 2001) and metastatic potential (Lemieux et al 1997) by acting in different capacities in cells. For example, by acting as a molecular chaperone, Hsp-27 can maintain integrity of cellular proteins under stressful conditions (Hartl and Hayer-Hartl 2002;Nollen and Morimoto 2002;Tavaria et al 1996) but can also enhance cell survival directly by modulating the apoptotic machinery (Concannon et al 2003;Farooqui-Kabir et al 2004;Latchman 2002).…”

Section: Introductionmentioning

confidence: 99%

Hsp-27 induction requires POU4F2/Brn-3b TF in doxorubicin-treated breast cancer cells, whereas phosphorylation alters its cellular localisation following drug treatment

Fujita

Ounzain

Wang

et al. 2011

Cell Stress and Chaperones

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POU4F2/Brn-3b transcription factor (referred to as Brn-3b) is elevated in >60% of breast cancers and profoundly alters growth and behaviour of cancer cells by regulating distinct subsets of target genes. Previous studies showed that Brn-3b was required to maximally transactivate small heat shock protein, HSPB1/Hsp-27 (referred to as , and consequently, Brn-3b expression correlated well with Hsp27 levels in human breast biopsies. In these studies, we showed that Brn-3b is increased in MCF7 breast cancer cells that survive following treatment with chemotherapeutic drug doxorubicin (Dox) with concomitant increases in Hsp-27 expression. Targeting of Brn3b using short interfering RNA reduced Hsp-27 in Doxtreated cells, suggesting that Brn-3b regulates Hsp-27 expression under these conditions. Wound healing assays showed increased Brn-3b in Dox-treated migratory cells that also express Hsp-27. Interestingly, Hsp-27 phosphorylation and cellular localisation are also significantly altered at different times following Dox treatment. Thus, phosphoHsp-27 (p-Hsp27) protein displayed widespread distribution after 24 hrs of Dox treatment but was restricted to the nucleus after 5 days. However, in drug-resistant cells (grown in Dox for >1 month), p-Hsp-27 was excluded from nuclei and most of the cytoplasm and appeared to be associated with the cell membrane. Studies to determine how this protein promotes survival and migration in breast cancer cells showed that the protective effects were conferred by unphosphorylated Hsp-27 protein.

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“…More recently, another group of DNA repair-associated proteins, the Fanconi anemia (FA) complementing proteins, have also been shown to contribute to cisplatin resistance in ovarian cancer via the FA-BRCA pathway and the use of inhibitors of the FA/BRCA pathway could restore sensitivity to platinum agents [11]. Other significant studies further elaborate on various aspects of cisplatin resistance, such as those showing that multidrug-resistant proteins, MDR1 (also referred to as P-glycoprotein) and MRP1 [12,13], MDM2 [14], and some heat-shock proteins (HSP27 and HSP70) [15] were all differentially expressed in cisplatin-resistant human ovarian carcinoma cells and have been suggested to play roles in acquired drug resistance. Also, overexpression of the copper transporter proteins ATP7A and ATP7B [16,17] and down-regulation of the copper influx transporter CTR1 [18,19] were also associated with platinum-based drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label‐free LC/MS‐based protein quantification method

Fitzpatrick

You²,

Bemis³

et al. 2007

Proteomics Clinical Apps

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Platinum-based chemotherapy, such as cisplatin, is the primary treatment for ovarian cancer. However, drug resistance has become a major impediment to the successful treatment of ovarian cancer. To date, the molecular mechanisms of resistance to platinum-based chemotherapy remain unclear. In this study, we applied an LC/MS-based protein quantification method to examine the global protein expression of two pairs of ovarian cancer cell lines, A2780/A2780-CP (cisplatin-sensitive/cisplatin-resistant) and 2008/2008-C13*5.25 (cisplatin-sensitive/cisplatinresistant). We identified and quantified over 2000 proteins from these cell lines and 760 proteins showed significant expression changes with a false discovery rate of less than 5% between paired groups. Based on the results we obtained, we suggest several potential pathways that may be involved in cisplatin resistance in human ovarian cancer. This study provides not only a new proteomic platform for large-scale quantitative protein analysis, but also important information for discovery of potential biomarkers of cisplatin resistance in ovarian cancer. Furthermore, these results may be clinically relevant for diagnostics, prognostics, and therapeutic improvement for ovarian cancer treatment.

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Heat shock protein 27 was up-regulated in cisplatin resistant human ovarian tumor cell line and associated with the cisplatin resistance

Cited by 75 publications

References 19 publications

Molecular mechanisms of cisplatin resistance

Molecular mechanisms of cisplatin resistance

Hsp-27 induction requires POU4F2/Brn-3b TF in doxorubicin-treated breast cancer cells, whereas phosphorylation alters its cellular localisation following drug treatment

Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label‐free LC/MS‐based protein quantification method

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