Heat shock proteins in human cancer

Sarto, Cecilia; Binz, Pierre Alain; Mocarelli, Paolo

doi:10.1002/(sici)1522-2683(20000401)21:6<1218::aid-elps1218>3.0.co;2-h

Cited by 125 publications

(67 citation statements)

References 125 publications

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“…This molecular chaperone protein is involved in various cellular stress responses, apoptosis and actin reorganization, but more significantly, it has been shown to be overexpressed in numerous human cancers, including invasive ductal carcinoma of the breast (reviewed in Ref. 8). Interestingly, Hsp70, another member of the heat shock protein family dysregulated in cancer (8), was down-regulated in the ErbB-2-overexpressing cell line.…”

Section: D-dige Analysis Of Breast Cancer Cell Linessupporting

confidence: 84%

Evaluation of Two-dimensional Differential Gel Electrophoresis for Proteomic Expression Analysis of a Model Breast Cancer Cell System

Gharbi

Gaffney

Yang

et al. 2002

Molecular & Cellular Proteomics

267

211

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The technique of fluorescent two-dimensional (2D) difference gel electrophoresis for differential protein expression analysis has been evaluated using a model breast cancer cell system of ErbB-2 overexpression. Labeling of paired cell lysate samples with N-hydroxy succinimidyl ester-derivatives of fluorescent Cy3 and Cy5 dyes for separation on the same 2D gel enabled quantitative, sensitive, and reproducible differential expression analysis of the cell lines. SyproRuby staining was shown to be a highly sensitive and 2D difference gel electrophoresis-compatible method for post-electrophoretic visualization of proteins, which could then be picked and identified by matrixassisted laser-desorption ionization mass spectroscopy. Indeed, from these experiments, we have identified multiple proteins that are likely to be involved in ErbB-2-mediated transformation. A triple dye labeling methodology was used to identify proteins differentially expressed in the cell system over a time course of growth factor stimulation. A Cy2-labeled pool of samples was used as a standard with all Cy3-and Cy5-labeled sample pairs to facilitate cross-gel quantitative analysis. DeCyder (Amersham Biosciences, Inc.) software was used to distinguish clear statistical differences in protein expression over time and between the cell lines. Molecular & Cellular Proteomics 1:91-98, 2002.The ability to determine statistically significant alterations in protein expression that correlate with disease or occur consequent to experimentally induced changes in cells is fundamental to the exploitation of proteomics. Previous studies from our laboratory have used two-dimensional (2D) 1 gel analysis of immunomagnetic affinity-sorted primary human breast cells to establish the protein expression profiles of luminal and myoepithelial cells (1). These differential expression studies were carried out using replicate 2D gels of each sample and post-staining with a fluorescent protein dye. The subsequent detailed curation and correlation of images was used to derive data sets for statistical analysis. This approach was attractive, because the fluorescent protein stain has a wide linear range of detection, thus giving improved quantification of both high and low abundance proteins. However, in these experiments, many pairs of gels were required to establish statistically significant differences in protein expression as each gel contains inherent experimental variations that limit image superimposition.The introduction of fluorescent 2D differential gel electrophoresis (DIGE) by Unlu et al. (2) has now made it possible to detect and quantitate differences between experimental pairs of samples resolved on the same 2D gel. The basis of the technique is the use of two mass-and charge-matched Nhydroxy succinimidyl ester derivatives of the fluorescent cyanine dyes Cy3 and Cy5, which possess distinct excitation and emission spectra. These are used to differentially label lysine residues of two protein samples for comparative analysis of the mixed sample on one gel. The ab...

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Section: D-dige Analysis Of Breast Cancer Cell Linessupporting

confidence: 84%

Evaluation of Two-dimensional Differential Gel Electrophoresis for Proteomic Expression Analysis of a Model Breast Cancer Cell System

Gharbi

Gaffney

Yang

et al. 2002

Molecular & Cellular Proteomics

267

211

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“…The UDP-Glc-deficient cell line used in this study has features resembling those of tumor cells from the ischemic regions. Mitochondrial and ER chaperones are often up-regulated in solid tumors both in experimental models and clinical samples (63,64). As in UDP-Glc-deficient cells, NF B is activated in many tumor cells, and the NF B activation is believed to have an important survival function (65)(66)(67).…”

Section: Udp-glc-deficient Cells As Model For Tumormentioning

confidence: 54%

A Cellular UDP-glucose Deficiency Causes Overexpression of Glucose/Oxygen-regulated Proteins Independent of the Endoplasmic Reticulum Stress Elements

Flores-Dı́az

Higuita

Florin

et al. 2004

Journal of Biological Chemistry

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A low level of UDP-Glc occurs in cells exposed to hypoxia or glucose starvation. This work reveals that a 65% reduction in the cellular UDP-Glc level causes upregulation of the mitochondrial chaperone GRP75 and the endoplasmic reticulum (ER) resident chaperones GRP58, ERp72, GRP78, GRP94, GRP170, and calreticulin. Conditions that cause misfolding of proteins within the ER activate the transcription factors ATF6␣/␤ and induce translation of the transcription factors XBP-1/ TREB5 and ATF4/CREB2. These transcription factors induce the overexpression of ER chaperones and CHOP/ GADD153. However, the 65% decrease in the cellular UDP-Glc level does not cause activation of ATF6␣, splicing of XBP-1/TREB5, induction of ATF4/CREB2, or expression of CHOP/GADD153. The activity of the promoters of the ER chaperones is increased in UDP-Glcdeficient cells, but the activity of the CHOP/GADD153 promoter is not affected, in comparison with their respective activities in cells having compensated for the UDP-Glc deficiency. The results demonstrate that the unfolded protein response remains functionally intact in cells with a 65% decrease in the cellular UDP-Glc level and provide evidence that this decrease is a stress signal in mammalian cells, which triggers the coordinate overexpression of mitochondrial and ER chaperones, independently of the ER stress elements.

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“…The heat shock proteins, including Hsp27, have been implicated in numerous diseases, including cancer (Sarto et al, 2000). In human cancers, posttranslational modifications, including phosphorylation of HSPs, has been commonly observed and often associated with particular types of malignancies (Sarto et al, 2000).…”

Section: Identification Of Phosphorylation Sites In Hsp27mentioning

confidence: 99%

“…In human cancers, posttranslational modifications, including phosphorylation of HSPs, has been commonly observed and often associated with particular types of malignancies (Sarto et al, 2000). Different intensity and migration of Hsp27 spots were observed in FHA and glioblastoma cells lines on 2D gels (Fig.…”

Section: Identification Of Phosphorylation Sites In Hsp27mentioning

confidence: 99%

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Identification of differentially expressed proteins in human glioblastoma cell lines and tumors

Zhang

Tremblay

McDermid

et al. 2003

Glia

112

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KEY WORDSproteomics; matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF); liquid chromatography tandem mass spectrometry (LC-MS-MS); glioblastoma; U87MG; major vault protein; cystatin B; Hsp27; tissue transglutaminase; epidermal growth factor receptor ABSTRACT An in-frame deletion of 801 bp in exons 2-7 (type III mutation) of the epidermal growth factor receptor (EGFR) is detected at high incidence in primary glioblastoma tumors. A proteomic approach was used to generate differential protein expression maps of fetal human astrocytes (FHA), human glioblastoma cell lines U87MG and U87MG expressing type III EGFR deletion (U87MG⌬EGFR) that confers high malignancy to tumor cells. Two-dimensional gel electrophoresis followed by in-gel digestion of separated spots and protein identification by LC-MS-MS and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) identified 23 proteins expressed at higher levels or exclusively in FHA and 29 proteins expressed at higher levels or exclusively in U87MG cells. Three proteins, ubiquitin, cystatin B, and tissue transglutaminase (TTG), were upregulated in U87MG⌬EGFR relative to U87MG. Four proteins highly expressed by U87MG cells, Hsp27, major vault protein, TTG, and cystatin B, were analyzed by Western blot, ELISA, or RT-PCR in cell extracts and in tissue samples of glioblastoma multiforme (GBM; grade IV), low-grade astrocytomas (grades I and II), and nonmalignant brain lesions. All four proteins were highly expressed in GBM tissues compared to nonmalignant brain. These proteins may be used as diagnostic or functional (e.g., multiple drug resistance, invasiveness) markers for glioblastoma tumors. GLIA 42:194 -208, 2003.

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Heat shock proteins in human cancer

Cited by 125 publications

References 125 publications

Evaluation of Two-dimensional Differential Gel Electrophoresis for Proteomic Expression Analysis of a Model Breast Cancer Cell System

Evaluation of Two-dimensional Differential Gel Electrophoresis for Proteomic Expression Analysis of a Model Breast Cancer Cell System

A Cellular UDP-glucose Deficiency Causes Overexpression of Glucose/Oxygen-regulated Proteins Independent of the Endoplasmic Reticulum Stress Elements

Identification of differentially expressed proteins in human glioblastoma cell lines and tumors

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