Genes and genetic networks responsive to mild hyperthermia in human lymphoma U937 cells

Tabuchi, Yoshiaki; Takasaki, Ichiro; Wada, Shigehito; Zhao, Qing‐Li; Hori, Takeshi; Nomura, Takaharu; Ohtsuka, Kenzo; Kondo, Takashi

doi:10.1080/02656730802140777

Cited by 43 publications

(54 citation statements)

References 40 publications

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“…Recent DNA microarray and computational microarray analyzing technologies have provided a view of the expression (9,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). It is well known that cancer cells exposed to HT of more than 42.5˚C will undergo cell death, whereas exposure to MHT conditions, i.e., temperatures up to 42.5˚C, produces only slight or no cytotoxicity (26).…”

Section: Introductionmentioning

confidence: 99%

Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells

Tabuchi

Wada

Furusawa³

et al. 2011

Int J Mol Med

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Abstract. Local hyperthermia (HT) for various types of malignant tumors has shown promising antitumor effects. To confirm the detailed molecular mechanism underlying cell death induced by HT, gene expression patterns and gene networks in human oral squamous cell carcinoma (OSCC) cells were examined using a combination of DNA microarray and bioinformatics tools. OSCC HSC-3 cells were treated with HT at 44˚C for 90 min or mild hyperthermia (MHT) at 42˚C for 90 min, followed by culturing at 37˚C for 0-24 h. Treatment of cells with HT prevented cell proliferation (62%) and induced cell death (17%), whereas these alterations were not observed in cells treated with MHT. Microarray analysis revealed substantial differences with respect to gene expression patterns and biological function for the two different hyperthermic treatments. Moreover, we identified the temperature-specific gene networks D and H that were obtained from significantly up-regulated genes in the HT and MHT conditions, respectively, using Ingenuity pathway analysis tools. Gene network D, which contains 14 genes such as ATF3, DUSP1 and JUN, was associated with relevant biological functions including cell death and cellular movement. Gene network H, which contains 13 genes such as BAG3, DNAJB1 and HSPA1B, was associated with cellular function and maintenance and cellular assembly and organization. These findings provide a basis for understanding the detailed molecular mechanisms of cell death elicited by HT in human OSCC cells. IntroductionIn the treatment of oral squamous cell carcinoma (OSCC), treatment outcomes have improved in the past two decades due to progress in reconstructive techniques, stereotactic radiotherapy, new anticancer drugs such as taxanes, and combinations of these therapeutic modalities (1). Nonetheless, it is well known that patients with advanced tumors or tumor recurrence have a poor prognosis with a median survival period less than one year (2). Local hyperthermia (HT) for various malignant tumors including OSCC has been recognized as an effective and attractive tool with the advantages of relatively few side effects and slight damage to normal tissue. Combinations of HT with chemotherapy, radiotherapy or both have been clinically used for patients with cancer in various organs, and their antitumor effects have been verified by many clinical trials (3-7).In general, HT elicits a wide spectrum of stress responses such as induction of heat shock proteins (HSPs), protein aggregation, an imbalance of protein homeostasis, DNA and RNA damage, reactive oxygen species production, cell growth arrest and cell death in mammalian cells (8,9). In particular, HSPs, which are induced by heat, behave as molecular chaperones and exert strong cytoprotective effects that prevent cell death. The treatment of cells with HT induces numerous signal transduction pathways which contribute variously to cell death and survival (10-12). Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown.Re...

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Section: Introductionmentioning

confidence: 99%

Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells

Tabuchi

Wada

Furusawa³

et al. 2011

Int J Mol Med

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“…It is well known that the mobility shift of HSF1 due to its phosphorylation indicates the activation of the molecule (31). In U937 cells, the elevated expression of HSPs such as Hsp70, Hsp40 and Hsp27 was observed following the activation of HSF1 under both non-apoptotic and apoptotic conditions (19,26). At 42˚C for 15 min, a transient mobility shift of HSF1 was observed at 0 and 0.5 h after the treatment.…”

Section: Resultsmentioning

confidence: 93%

“…Time-course changes of the expression of HSPs by microarray at both 42 and 44˚C were comparable to those from western blot analysis and quantitative real-time PCR analyses. Induction of HSPs is a common response to heat with or without cell death, including apoptosis, as described in several microarray studies (17)(18)(19)(21)(22)(23)(24)(25)(26)(27). HSPs have been shown to block apoptosis by interfering with caspase activation and to inhibit apoptosis directly or indirectly (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…1C). markedly induced apoptosis, whereas heat stress at 41-42˚C for <30 min induced no cell damage in human leukemia U937 cells (20,(26)(27)(28). on the other hand, treatment of U937 cells for relatively long periods of 60-120 min at 42˚C significantly elicited apoptosis (19,28).…”

Section: Discussionmentioning

confidence: 99%

“…Several investigators have indicated that heat stress affects the expression pattern of genes in many kinds of cell types with a cell death or no cell death condition (17-27). In addition, bioinformatics analysis have shown that differentially expressed genes influenced by heat could be sorted into several functional categories such as molecular chaperones, cell death, protein degradation, transcription, signal transduction and membrane transport (10,17,19,22,23,26). As described above, because heat stress induces complex cellular responses and changes in signal transduction, the mechanisms of heat response have not been elucidated in detail.…”

Section: Introductionmentioning

confidence: 99%

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Identification of biological functions and gene networks regulated by heat stress in U937 human lymphoma cells

et al. 2011

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Abstract. although cancer cells exposed to temperatures >42.5˚C undergo cell death as the temperature rises, exposure of up to 42.5˚C induces slight or no cytotoxicity. The temperature of 42.5˚C is, therefore, well known to be the inflection point of hyperthermia. To better understand the molecular mechanisms underlying cellular responses to heat stress at temperatures higher and lower than the inflection point, we carried out global scale microarray and computational gene expression analyses. Human leukemia U937 cells were incubated at 42˚C or 44˚C for 15 min and cultured at 37˚C for 0-6 h. Apoptosis accompanied by the activation of caspase-3 and DNA fragmentation was only observed in cells treated with heat stress at 44˚C, but not at 42˚C. Although a large number of genes were differentially expressed by a factor of 2.0 or greater, we found substantial differences with respect to the biological functions and gene networks of the genes differentially expressed at the two temperatures examined. Interestingly, we identified temperature-specific gene networks that were considered to be mainly associated with cell death or cellular compromise and cellular function and maintenance at 44˚C or 42˚C, respectively, by using the Ingenuity pathway analysis tools. These findings provide the molecular basis for a further understanding of the mechanisms of the biological changes that are responsive to heat stress in human lymphoma cells.

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Genes and genetic networks responsive to mild hyperthermia in human lymphoma U937 cells

Cited by 43 publications

References 40 publications

Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells

Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells

Identification of biological functions and gene networks regulated by heat stress in U937 human lymphoma cells

Impact of Climate Change on Livestock Production

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