High constitutive expression of heat shock protein 90α in human acute leukemia cells

Yufu, Yuji; Nishimura, Junji; Nawata, Hajime

doi:10.1016/0145-2126(92)90008-u

Cited by 135 publications

(87 citation statements)

References 26 publications

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“…Overall, the median expression of hsp90 was higher in ALL patients compared to peripheral blood mononuclear cells (PBMC) of healthy volunteers (Figures 2 and 3). This confirms data published by Yufu et al, 27 who found higher hsp90 protein expression in leukaemic cell lines as compared to PBMC. The reason for the upregulation of hsp90 in leukaemic cells has been suggested to be associated with cell differentiation and/or cell proliferation.…”

Section: Resultssupporting

confidence: 82%

Expression of heat-shock protein 90 in glucocorticoid-sensitive and -resistant childhood acute lymphoblastic leukaemia

et al. 2003

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Early reduction of leukaemic cells by chemotherapy is a strong predictor for treatment outcome in childhood acute lymphoblastic leukaemia (ALL). In ALL-(Berlin-Frankfurt-Mü nster) trials, early treatment response is assessed by the in vivo response to glucocorticoids (prednisone response, PR), the molecular background of which is unknown. The intracellular effects of glucocorticoids (GCs) are mediated by the glucocorticoid receptor (GR). In the absence of GC, the inactive GR resides within a multiprotein complex, consisting predominantly of the chaperone protein hsp90 (heat-shock protein 90). Until now, studies targeting GC resistance mainly focused on GR disorders and alterations of genes known to be associated with drug resistance. In addition, the GR multiprotein complex was associated with GC resistance in in vitro studies. We performed a case-control study for PR to investigate the association of in vivo GC resistance and hsp90 expression in childhood ALL. Hsp90 expression was assessed using a realtime PCR approach (Taqman technology) and Western blot technology. In this setting, we found no association of in vivo GC resistance and hsp90 expression. Therefore, we conclude that the expression of hsp90, the major component of the GR activating complex, is of minor importance for the in vivo GC resistance in childhood ALL.

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Section: Resultssupporting

confidence: 82%

Expression of heat-shock protein 90 in glucocorticoid-sensitive and -resistant childhood acute lymphoblastic leukaemia

et al. 2003

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“…In connection with the changes of Grp94 gene expression of colorectal carcinoma cells upon SB tratment, it is interesting to note that several studies have suggested that HSPs play some roles during cell growth and cell differentiation of tumor. The expression of the Hsp90 gene was enhanced in the leukemia cell lines and the acute leukemia cells as compared with normal mononuclear cells, but was markedly suppressed after tumor growth inhibition [5]. Continuous expression of HSPs proteins in tumor cells may be required to serve as molecular chaperones in regulating and stabilizing tumor growth process.…”

Section: Discussionmentioning

confidence: 98%

“…Briefly, 5 10 4 /ml cells were inoculated onto a 96-well plates in 100 l regular medium per well and after 24 h culture, the cells of each well were exposed to SB to a final concentration of 2 m M and 4 m M for 2 d and 4 d respectively. At the end of the exposure, 10 μl (5 mg/ml) MTT in PBS was then added.…”

Section: Mtt Assaymentioning

confidence: 99%

“…The most prominent HSPs of mammalian cells have molecular weights of approximately 90,000 (HSP90), and 70,000 (HSP70) [1], [3]. Many studies have suggested a possible correlation between the expression of HSPs and the growth and differentiation of tumor cells [4][5][6][7][8][9]. Recent evidence revealed that considerable expression of HSPs is found in non-heat-shocked cells, showing that HSPs may be induced by other stresses and participated in broader body defense and even in normal growth and development [10].…”

Section: Introductionmentioning

confidence: 99%

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The expression of glucose regulated protein-94 in colorectal carcinoma cells treated by sodium butyrate

Jin

2000

Cell Res

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The expression of glucose regulated protein 94 (GRP94) during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at G 0 /G 1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.

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“…The chaperone molecule HSP-70 had a relatively low mRNA expression level, while the mRNA expression level of HSP-90 was relatively high (2000-fold higher than HSP-70 expression), which is in concordance with earlier studies reporting protein and mRNA levels of HSP-90 and HSP-70 in acute leukemias. 10,18,19 As HSP-70 is part of the more immature GR-(co)chaperone complex, its low expression level might determine a ratelimiting step in the initial maturation process of the GR. For none of the (co)chaperone molecules as tested in this study, a relation between mRNA expression level and in vitro GC resistance was found.…”

Section: Discussionmentioning

confidence: 99%

mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL

et al. 2005

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Resistance to glucocorticoids (GC) is an important adverse risk factor in the treatment of acute lymphoblastic leukemia (ALL). To induce apoptosis, GC bind to the GC receptor (GR), which is regulated by various (co)chaperone proteins such as heatshock protein 70 (HSP-70), HSP-40, HIP (HSP-70-interacting protein), BAG-1 (BCL-2-associated gene product-1), HOP (HSP-70/HSP-90-Organizing protein), HSP-90, P-23, FKBP-51, FKBP-52 and CYP-40. In this study, we tested the hypothesis that mRNA expression levels of these molecules are determinants of GC resistance in childhood ALL. In all, 20 children with ALL cells in vitro sensitive to prednisolone (LC 50 o0.1 lg/ml) were compared each with a resistant patient (LC 50 4150 lg/ml), matched for immunophenotype, age and white blood cell count. mRNA expression levels of the (co)chaperone molecules were measured by quantitative real-time RT-PCR and normalized to GAPDH and RNaseP levels. In vitro resistance to prednisolone was measured by MTT assay. HSP-90 mRNA expression levels were 2000-fold higher as compared to HSP-70. Using matched pair analysis, mRNA expression levels of the various (co)chaperone molecules were not significantly different between in vitro-sensitive and -resistant patients. GC resistance in childhood ALL cannot be attributed to different mRNA expression levels of the investigated (co)chaperone molecules involved in GC binding and transport to the nucleus.

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High constitutive expression of heat shock protein 90α in human acute leukemia cells

Cited by 135 publications

References 26 publications

Expression of heat-shock protein 90 in glucocorticoid-sensitive and -resistant childhood acute lymphoblastic leukaemia

Expression of heat-shock protein 90 in glucocorticoid-sensitive and -resistant childhood acute lymphoblastic leukaemia

The expression of glucose regulated protein-94 in colorectal carcinoma cells treated by sodium butyrate

mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL

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