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Gene expression profiles of mammary epithelial and breast cancer cells following fever range hyperthermia

ABSTRACT: Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45oC) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray analysis of the global transcription changes was subsequently performed.

ORGANISM(S): Homo sapiens

PROVIDER: GSE48398 | GEO | 2013/12/01

SECONDARY ACCESSION(S): PRJNA209945

REPOSITORIES: GEO

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Gene expression profiles of mammary epithelial and breast cancer cells following fever range hyperthermia

Project description:Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45oC) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray analysis of the global transcription changes was subsequently performed. MCF10A (mammary epithelial cells) and MCF7, MDA231, and MDA468 breast cancer cells were grow at normal growth temperatures or subjected to 30 minutes of hyperthermic (45oC) shock followed by replacement with conditioned media at normal growth temperatures. RNA was collected 4 hours after shock and subjected to microarray analysis.

2013-12-01 | E-GEOD-48398 | biostudies-arrayexpress

Comprehensive multi-omics analysis revealed WEE1 as a synergistic lethal target with hyperthermia through CDK super-activation

Project description:The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer (EOC) is still controversial partly because of the poorly understood mechanism of action. Further an understanding of the underlying mechanisms could identify potential combination therapies. Here, we conduct a comprehensive multi-omics study (transcriptiome, proteome, and phosphoproteome) upon hyperthermia (HT) in ovarian cancer cells. Unbiased trans-omics approach deciphered a unique hyperthermia- induced molecular panorama and demonstrated rapid alterations in protein phosphorylation as the primary cell response upon HT. Based on the phospho-signature, we identified CDK kinases to be hyperactivated and responsible for the global signaling landscape upon HT. Molecular and functional experiments demonstrated the dynamic and reversible CDK activity, subsequent replication arrest, and early mitotic entry after HT. A follow-up drug screen identified WEE1 inhibition to synergistically kills cancer cells with HT. An in-house developed miniaturized devise delivered proof-of-concept that the combination of hyperthermia with WEE1i leads to dramatic anti-tumor responses in vivo. These findings provide new insights into how to improve the effectiveness of HIPEC in EOC.

2023-12-12 | PXD040849 | Pride

Molecular determinants of tumor response to hyperthermia

Project description:A deeper mechanistic understanding of response to hyperthermia in cancer cells in comparison between hyperthermia sensitive and resistant ovarian cancer cell lines

2016-12-31 | GSE77310 | GEO

Identification of genes responsive to mild hyperthermia in human leukemia U937 cells

Project description:The rationale underlying hyperthermia is the fact that temperatures over 42.5˚C are highly cytotoxic to tumor cells. On the other hand, although mild hyperthermia at a range from 39 to 41˚C alone did not induce cytotoxicity in tumor cells, mild hyperthermia is reported to show a synergism with radiotherapy and anti-cancer drugs. Here, the effects of mild hyperthermia (41˚C for 30 min) on the gene expression in human lymphoma U937 cells were investigated using by an Affymetrix GeneChip system. Although the cells treated with the mild hyperthermia did not induce apoptosis, a significant increase in protein levels of heat shock proteins, Hsp40 and Hsp70, was observed following activation of heat shock factor-1. At 3 h post-treatment, 938 probe sets that were differentially expressed by >1.5-fold were identified. Keywords: mild hyperthermia, gene expression, Human lymphoma U937 cell

2008-01-03 | GSE10043 | GEO

Identification of genes responsive to mild hyperthermia in human normal fibroblast OUMS-36 cells

Project description:Hyperthermia is widely used to treat patients with various cancers. Here, the effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in OUMS-36 human normal fibroblast cells were investigated using an Affymetrix GeneChip system. The cells were treated with mild hyperthermia, followed by incubation for 0, 1, or 3 h at 37°C. No cell death was observed in the mild hyperthermia-treated cells. On the other hand, many genes that were differentially expressed by a factor 1.5 or greater were identified in the cells treated with the mild hyperthermia.

2012-07-13 | GSE39178 | GEO

Identification of genes responsive to mild hyperthermia in human skin normal fibroblast Hs68 cells

Project description:Hyperthermia is widely used to treat patients with various cancers. Here, the effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in Hs68 human skin normal fibroblast cells were investigated using an Affymetrix GeneChip system. The cells were treated with mild hyperthermia, followed by incubation for 0, 1, or 3 h at 37°C. No cell death was observed in the mild hyperthermia-treated cells. On the other hand, many genes that were differentially expressed by a factor 1.5 or greater were identified in the cells treated with the mild hyperthermia.

2012-07-13 | GSE39177 | GEO

Effect of mild hyperthermia on Mk differentiation

Project description:Physical factors can have major influences on the proliferation and differentiation fate of hematopoietic stem cells in culture. Recently, we demonstrated that cord blood CD34+ cells undergo accelerated and increased megakaryocyte differentiation when incubated at 39°C. In this study, we investigated in detail the impacts of mild hyperthermia on the kinetics of megakaryocyte differentiation, maturation, polyploidization and cell viability. The qualitative and quantitative effects on Mk differentiation were found to be rapidly induced, and optimization of the culture length at 39°C led to greater Mk yields. Mild hyperthermia did not promote endomitosis of cord blood-derived Mk, but rather led to a small reduction in the proportion of polyploid Mk. Moreover, it had little impact on viability but induced a significant shift in the proportion of cells undergoing apoptosis at 37°C to necrosis at 39°C. Finally, our results suggest that the effects on megakaryocyte differentiation could be the consequences of aberrant expression of key megakaryocyte transcription factors induced by mild hyperthermia. Keywords: Effect of mild hyperthermia on Mk differentiation

2007-12-01 | GSE9218 | GEO

Identification of genes responsive to hyperthermia in human leukemia U937 cells

Project description:Hyperthermia (41˚C <) is widely used to treat patients with various cancers. Here, the effects of hyperthermia (42˚C for 90 min) on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with hyperthermia (42°C for 90 min) and followed by incubation for 0, 1, 3 or 6 h at 37°C. The percentage of DNA fragmentation was 7.5 ± 0.9 (mean ± SD), 10.1 ± 0.2, and 17.3 ± 2.3 at the incubation periods of 1, 3, and 6 h, respectively. Of approximately 47,000 probe sets analyzed, the hyperthermia down-regulated 4,214 probe sets and up-regulated 1,334 by a factor 2.0 or greater.

2008-11-11 | GSE13503 | GEO

Molecular determinants of tumor response to hyperthermia

Project description:Proteomic data from ovarian cancer cells (A2780 and SKOV3); treated cells with or without hyperthermia (46 deg C for 1 hr); 2 biological replicates for each cell line/condition

2018-10-22 | PXD005055 | Pride

Subsets of NFkappaB-dependent genes are differentially regulated after combined treatment with hyperthermia and cytokine

Project description:Heat shock transcription factor 1 (HSF1) is responsible for triggering stress-induced activation of the HSP genes. HSF1 is also involved in the regulation of many other genes associated with multiple cellular processes including cell signaling, development, fertility, cell death and metabolism, e.g. NFkappaB transcription factor. Here we aimed to establish a global picture for the association between hyperthermia-modulated expression of NFkappaB-dependent genes and HSF1 binding in regulatory regions of target genes. The global pattern of HSF1 binding was analyzed after 10 and 20 minutes of hyperthermia using the ChIP-Seq approach. The analysis revealed about 25,000 HSF1 binding sites in chromatin of control untreated U-2 OS cells, which nearly doubled in cells subjected to hyperthermia. The presence of hyperthermia-induced HSF1 binding was established in regulatory regions of hyperthermia-affected genes and in TNF-affected genes. In most cases hyperthermia pre-conditioning inhibited cytokine-mediated activation of NF-κB-dependent genes. However, our results also revealed novel gene subsets that included TNFalpha-regulated and hyperthermia-unaffected genes, as well as genes (co)repressed, (co)stimulated, or antagonized by both types of stimuli.

2015-08-01 | GSE60984 | GEO

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