scholarly journals Generation of tumors in wing imaginal discs of Drosophila melanogaster third instar larvae to study temporal and spatial patterns of expression of major heat shock proteins

2021 ◽  
Author(s):  
Gunjan Singh ◽  
Subhash C. Lakhotia
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Spatial Patterns ◽  
Hsp70 Expression ◽  
Loss Of Function ◽  
Temporal And Spatial Patterns ◽  
Early Stages ◽  
Temporal And Spatial ◽  
Shock Proteins

Cancer cells experience a variety of stresses like hypoxia, lack of nutrients, DNA damage and immune responses, which trigger several processes to drive genomic instability and mutation, alterations in gene expression programs, and reprogramming of the metabolic pathways to escape growth inhibition signaling, and acquire resistance to the immune surveillance. Different heat shock proteins are expressed at elevated levels in cancer cells. However, their specific roles in initiation, establishment and progression of cancers are still not clear. Here using the loss of function allele of the apico-basal polarity gene, lgl, we have established models for induction of tumorous somatic clones of different genetic constitutions at defined developmental times for examination of temporal and spatial patterns of expression of the major heat shock protein families, namely Hsp83, Hsp70, Hsp60 and Hsp27. The Hsp83, Hsp60 and Hsp27 begin to express in all cells of the tumor at high levels since early stages (48hr after tumor induction) and continue their high expression at later stages when the tumorous clones accumulate F-actin and get transformed. Levels of the heat shock cognate Hsc70 proteins also follow the same pattern as the other Hsps. However, the major stress-inducible Hsp70 is not expressed at early stages of tumor growth, but expresses at a later stage only in a few cells in a given lgl loss of function clone, which also shows high F-actin aggregates. Thus, the major Hsps, except the Hsp70, seems to be involved in early as well as late stages of epithelial tumors induced by loss of the Lgl cell polarity protein, while the Hsp70 expression in a few cells coincides with their getting transformed. This model will be useful for further genetic studies to dissect specific roles of different Hsps in tumor development and their therapeutic manipulation.

scholarly journals Hsps responsible for apoptosis induction failure in cervical cancer cells upon osthole and tamoxifen treatment

2019 ◽  
Vol 73 ◽  
pp. 563-571
Author(s):  
Joanna Jakubowicz-Gil ◽  
Roman Paduch ◽  
Krystyna Skalicka-Woźniak ◽  
Joanna Sumorek-Wiadro ◽  
Adrian Zając ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Cell Lines ◽  
Tamoxifen Treatment ◽  
Hpv 16 ◽  
Cervical Cancer Cells ◽  
Shock Proteins ◽  
Human Cervical Cancer

Aim: The aim of the present study was to investigate the efficacy of osthole (7-metoxy-8-isopenthenocoumarin) alone and combined with tamoxifen (TAM) in the elimination of human cervical cancer cells via programmed death. The involvement of heat shock proteins, i.e. well-known molecular chaperones, will be investigated. Material/Methods: Three human cervical cancer cell lines, infected with human papilloma virus (HPV), i.e. HeLa (HPV 18), SiHa (HPV 16), and CaSki (HPV 16 and 18), were used in the experiments. After osthole and TAM treatment, cells stained with fluorochromes were analyzed microscopically according to apoptotic, autophagic, and necrotic morphology. Hsp27, Hsp72, and Hsp90 levels were analyzed by immunoblotting. Transfection with specific siRNA was used for blocking of Hsp expression. Results: In the HeLa, CaSki, and SiHa cell lines, osthole and TAM applied alone had no significant effect on cell death induction. This was correlated with an overexpression of heat shock proteins 27, 72, and 90. In the case of a combination of both drugs, the level of apoptosis was elevated only in SiHa cells. Preincubation with osthole followed by TAM addition as well as simultaneous incubation with both drugs was the most effective. This was correlated with the inhibition of Hsp27, Hsp72, and Hsp90 expression. Blocking of Hsp expression with specific siRNA increased the sensitivity of the studied cell lines to the induction of apoptosis, but not to autophagy or necrosis. Conclusions: Our results indicated that the elimination of heat shock proteins from cervical cancer cells sensitized them to initiation of apoptosis after osthole and tamoxifen treatment.

Expression of heat shock proteins in medulloblastoma

2013 ◽  
Vol 12 (5) ◽  
pp. 452-457 ◽  
Author(s):  
George A. Alexiou ◽  
George Vartholomatos ◽  
Kalliopi Stefanaki ◽  
Amalia Patereli ◽  
Lefkothea Dova ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Significant Positive Correlation ◽  
Large Cell ◽  
Hsp70 Expression ◽  
Ki 67 ◽  
Positive Correlation ◽  
Wide Range ◽  
Shock Proteins ◽  
Multiplex Bead

Object Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis. Methods The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed. Results Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer15) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer82), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer15) and Ki-67 index (r = −0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076). Conclusions A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.

scholarly journals Disruption of Heat Shock Factor 1 Reveals an Essential Role in the Ubiquitin Proteolytic Pathway

2000 ◽  
Vol 20 (8) ◽  
pp. 2670-2675 ◽  
Author(s):  
Lila Pirkkala ◽  
Tero-Pekka Alastalo ◽  
XiaoXia Zuo ◽  
Ivor J. Benjamin ◽  
Lea Sistonen
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Hsp70 Expression ◽  
Heat Shock Factor 1 ◽  
Loss Of Function ◽  
Down Regulation ◽  
Proteolytic Pathway ◽  
Ubiquitin Proteasome ◽  
A Cell ◽  
Shock Proteins

ABSTRACT Inhibition of proteasome-mediated protein degradation machinery is a potent stress stimulus that causes accumulation of ubiquitinated proteins and increased expression of heat shock proteins (Hsps). Hsps play pivotal roles in homeostasis and protection in a cell, through their well-recognized properties as molecular chaperones. The inducible Hsp expression is regulated by the heat shock transcription factors (HSFs). Among mammalian HSFs, HSF1 has been shown to be important for regulation of the heat-induced stress gene expression, whereas the function of HSF2 in stress response is unclear. Recent reports have suggested that both HSF1 and HSF2 are affected during down-regulation of ubiquitin-proteasome pathway (Y. Kawazoe et al., Eur. J. Biochem. 255:356–362, 1998; A. Mathew et al., Mol. Cell. Biol. 18:5091–5098, 1998; D. Kim et al., Biochem. Biophys. Res. Commun. 254:264–268, 1999). To date, however, no unambiguous evidence has been presented as to whether a single specific HSF or multiple members of the HSF family are required for transcriptional induction of heat shock genes when proteasome activity is down-regulated. Therefore, by using loss-of-function and gain-of-function strategies, we investigated the specific roles of mammalian HSFs in regulation of the ubiquitin-proteasome-mediated stress response. Here we demonstrate that HSF1, but not HSF2, is essential and sufficient for up-regulation of Hsp70 expression during down-regulation of the ubiquitin proteolytic pathway. We propose that specificity of HSF1 could be an important therapeutic target during disease pathogenesis associated with abnormal ubiquitin-dependent proteasome function.

scholarly journals Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4407
Author(s):  
Jan Hrudka ◽  
Karolína Jelínková ◽  
Hana Fišerová ◽  
Radoslav Matěj ◽  
Václav Mandys ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Rank Test ◽  
Hsp70 Expression ◽  
Uicc Stage ◽  
Shock Proteins

Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan–Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson’s chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa (p = 0.014), and they occurred more often in female patients and vice versa (p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided (p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors (p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage (p = 0) and right sided localization (p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC.

scholarly journals Epigenetic Alterations of Heat Shock Proteins (HSPs) in Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4758 ◽  
Author(s):  
Hyun Ban ◽  
Tae-Su Han ◽  
Keun Hur ◽  
Hyun-Soo Cho
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Cytotoxic Agents ◽  
Epigenetic Alterations ◽  
Regulatory Processes ◽  
Physiological Processes ◽  
Epigenetic Modifiers ◽  
Epigenetic Machinery ◽  
Shock Proteins

Heat shock proteins (HSPs) are associated with various physiological processes (protein refolding and degradation) involved in the responses to cellular stress, such as cytotoxic agents, high temperature, and hypoxia. HSPs are overexpressed in cancer cells and play roles in their apoptosis, invasion, proliferation, angiogenesis, and metastasis. The regulation or translational modification of HSPs is recognized as a therapeutic target for the development of anticancer drugs. Among the regulatory processes associated with HSP expression, the epigenetic machinery (miRNAs, histone modification, and DNA methylation) has key functions in cancer. Moreover, various epigenetic modifiers of HSP expression have also been reported as therapeutic targets and diagnostic markers of cancer. Thus, in this review, we describe the epigenetic alterations of HSP expression in cancer cells and suggest that HSPs be clinically applied as diagnostic and therapeutic markers in cancer therapy via controlled epigenetic modifiers.

Calcium Phosphate Powder for Cancer Vaccination

2007 ◽  
Vol 361-363 ◽  
pp. 1207-1210 ◽  
Author(s):  
Patrick Frayssinet ◽  
Daniel Ciocca ◽  
Nicole Rouquet
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Cancer Tissue ◽  
Phosphate Powder ◽  
Cancer Vaccination ◽  
Shock Proteins ◽  
Antigen Presenting ◽  
Proteins And Peptides

Cancer cells synthesize abnormal proteins and peptides which are associated to heat shock proteins being overproduced by these cells due to the stress induced by the particular biology of cancer tissue. We have purified on hydroxylapatite powder heat shock proteins using the HAparticles as purification bed, vectors for the proteins and vaccination adjuvant. The powder make possible that the purified HSPs and their associated peptides are transfected to the antigen presenting cells and presented to the T cells for the destruction of the cancer cells bearing the antigens.

scholarly journals Protective effect of Zingiber zerumbet Smith extract on thermotolerance

2021 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Yasuhito Shirai ◽  
Hisakazu Kobayashi ◽  
Shuji Ueda ◽  
Yun Sang Soon ◽  
Akiho Kushiya ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Growth Rate ◽  
Heat Stress ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Hsp70 Expression ◽  
Heat Shock Treatment ◽  
Zingiber Zerumbet ◽  
Murine Liver ◽  
Shock Proteins

Background: Global warming causes severe heat conditions. Heat stress contributes to higher morbidity of heatstroke in human and mortality in livestock. To protect them from heat stress, thermotolerance mechanisms were widely studied, and some studies suggest relationship between heat shock proteins (HSPs) and thermotolerance. HSPs were not induced by only heat shock but also some stimulations including bioactive compounds from plants. Zingiber zerumbet is a perennial herb found in many tropical countries, including Thailand. The rhizome of Zingiber zerumbet contains zerumbone that is a bioactive compound to induce HSPs expression in animal cells.Objective: To prevent higher morbidity of heatstroke in human and mortality in livestock by the heat stress, we investigated the effect of zerumbone, the extract of Zingiber zerumbet Smith, on thermotolerance, using a cell line and mice.Methods: The murine liver hepatoma cell line, Hepa1c1c7 cells, were incubated in medium supplemented with extract from rhizome of Zingiber zerumbet Simith containing zerumbone, and then the expression of heat shock proteins (HSP) 40, 70 and 90 were investigated by western blotting. Furthermore, we established the evaluation system of thermotolerance using mice, and studied the effect of the extract on the growth rate of mice under the heat shock treatment. Briefly, 4 weeks old C57BL6 mice were fed that with the extract (or vehicle) for a week before the first heat shock treatment (38 °C for an hour). Before and after five days heat treatment, body weights were measured. The protein expressions of heat shock proteins in liver were measured by western blotting using HSPs antibodies.Results: The extract of Zingiber zerumbet rhizome, equivalent to 50 μM zerumbone, significantly increased the expression of heat shock proteins (HSP40, HSP70, HSP90). The growth rate of the mice under the heat treatment were lower than control. The feeding with the extract containing 25 ppm zerumbone have significantly attenuated the decline of the growth rate led by the heat treatment, whereas there was little effect on mouse growth rate grown under normal conditions. The protein expression of HSP70 in the liver of zerumbone-fed mice was upregulated compared with control mice, equivalent to heat treatment without zerumbone. On the other hand, both treatments of zerumbone and heat resulted in highest HSP70 expression among four groups.Conclusion: Our study demonstrated that oral administration of the extract of Zingiber zerumbet Smith led to the attenuation of decline of growth rate induced by heat treatment. HSP70 expression in murine liver was enhanced by either feeding the extract or heat treatment. More interestingly, HSP70 expression was further enhanced by both treatments of zerumbone and heat. These results suggested that zerumbone may contribute to thermotolerance via, at least, HSP70 expression.Keywords: Zingiber zerumbet, thermotolerance, heat shock protein

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