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accession-icon GSE54330
Interleukin-6 is a Potential Therapeutic Target in Interleukin-6 Dependent Estrogen Receptor-alpha Positive Breast Cancer [patient tumor tissue]
  • organism-icon Homo sapiens
  • sample-icon 36 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

Interleukin-6 (IL-6) is an important growth factor for estrogen receptor-alpha (ER) positive breast cancer, and elevated serum IL-6 is associated with poor prognosis. We firstly demonstrated that pSTAT3 is the primary downstream IL-6 signaling pathway in ER-positive breast cancer, using ten different breast cancer cell lines. Three-dimensional cultures of these cell lines were also used to develop a 17-gene IL-6 specific gene signature that could be used to identify IL-6 driven disease. This signature included a variety of genes involved in immune cell function and migration, cell growth and apoptosis, and the tumor microenvironment. To further validate this IL-6 signature, we obtained 36 human ER-positive breast cancer tumor samples with matched serum for gene expression profiling and determination of an IL-6 pathway activation score (PAS). Patients with high IL-6 PAS were also enriched for elevated serum IL-6 (>=10 pg/ml). We then utilized a murine MCF-7 xenograft model to determine the role of IL-6 in ER-positive breast cancer and potential anti-IL-6 therapy in vivo. When IL-6 was administered in vivo, MCF-7 cells engrafted without the need for estrogen supplementation. Subsequently, we prophylactically treated mice at MCF-7 engraftment with an anti-IL-6 antibody (siltuximab), fulvestrant or combination therapy. Siltuximab alone was able to blunt MCF-7 engraftment. Similarly, when tumors were allowed to grow to 125 mm3 before treatment, siltuximab alone demonstrated tumor regressions in 90% (9/10) of tumors. Given the established role for IL-6 in ER+ breast cancer, this data demonstrates the potential for anti-IL-6 therapeutics.

Publication Title

Interleukin-6 is a potential therapeutic target in interleukin-6 dependent, estrogen receptor-α-positive breast cancer.

Sample Metadata Fields

Specimen part

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accession-icon GSE47973
Expression data of LNCaP and MDA PCa 2b cells in absence or presence of IL6
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)

Description

Prostate cancer (PCa) development and progression are associated with chronic inflammation. The cytokine interleukin (IL)-6 can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL-6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, under treatment with 5 ng/ml IL-6. Interferon regulatory factor (IRF)9 was identified as one of the most prevalent IL-6 regulated genes in both cell lines. IRF9 is a mediator of type I interferon signaling and acts together with signal transduction and activator of transcription (STAT)1 and 2 to activate transcription of interferon responsive genes. The IL-6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and Western blot, respectively, in both cell lines and could be blocked by the anti-IL-6 antibody Siltuximab. Three PCa cell lines with an autocrine IL-6 loop, PC3, DU145, and LNCaP-IL-6+, showed a high expression of IRF9. A tissue microarray with 36 malignant and adjacent 36 benign areas from prostate cancer specimens showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL-6. Downregulation and overexpression of IRF9 provided evidence for an interferon-independent role of IRF9 on cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFN-2. We concluded that IL-6 is an inducer of IRF9 expression in prostate cancer and a sensitizer for the antiproliferative effects of IFN2.

Publication Title

IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE44053
Identification of heat stress-targets of translational control by large scale analysis of Arabidopsis trancriptome and translatome.
  • organism-icon Arabidopsis thaliana
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Heat stress is one of the most prominent and deleterious environmental threads affecting plant growth and development. Upon high temperatures, plants launch specialized gene expression programs that promote stress protection and survival. These programs involve global and specific changes at the transcriptional and translational levels. However the coordination of these processes and their specific role in the establishment of the heat stress response is not fully elucidated.

Publication Title

Analysis of genome-wide changes in the translatome of Arabidopsis seedlings subjected to heat stress.

Sample Metadata Fields

Specimen part

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accession-icon GSE34619
Gene expression profile in Barrett's esopahgus
  • organism-icon Homo sapiens
  • sample-icon 28 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Microarray was used to identify differential gene expression pattern in Barrett's esophagus (BE), compared to the normal adjacent epithelia gastric cardia (GC) and normal squamous esophagus (NE)

Publication Title

Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.

Sample Metadata Fields

Specimen part

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accession-icon SRP101622
Gene expression analysis of the effect of UV-B radiation in the growth zone of the maize leaf
  • organism-icon Zea mays
  • sample-icon 15 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 1500

Description

UV-B radiation affects leaf growth in a wide range of species. In this work, we demonstrate that UV-B levels present in solar radiation inhibits maize leaf growth without causing any other visible stress symptoms, including accumulation of DNA damage. We conducted kinematic analyses of cell division and expansion to understand the impact of UV-B radiation on these cellular processes. Our results demonstrate that the decrease in leaf growth is a consequence of a reduction in cell production, and a shortened growth zone (GZ) in UV-B irradiated leaves. To determine the molecular pathways involved in UV-B inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of control and UV-B exposed plants. Our results show a link between the observed leaf growth inhibition and the expression of specific cell cycle and developmental genes, including Growth Regulating Factors (GRFs) and transcripts for proteins participating in different hormone pathways. Overall design: Factorial design with two factors: Treatment (control vs UV-B) x Zone I (0-1cm from base of the leaf), 2 (1-2cm from base of the leaf) and 3 (2-3cm from base of the leaf), 3 replicates

Publication Title

UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and Gibberellin Levels.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE17511
Expression data from K5-IKKbeta transgenic mouse skin
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

IKKbeta is a subunit of the IkB kinase (IKK) complex required for NF-kB activation in response to pro-inflammatory signals. NF-kB regulates the expression of many genes involved in inflammation, immunity and apoptosis, and also controls cell proliferation and differentiation in different tissues; however, its function in skin physiopathology remains controversial. We here report the alterations caused by increased IKKbeta activity in basal cells of the skin of transgenic mice.

Publication Title

IKKbeta leads to an inflammatory skin disease resembling interface dermatitis.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE73509
CaSR modulator in neuroblastoma model
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 30 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Human Gene 2.1 ST Array (hugene21st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE73506
CaSR modulator in neuroblastoma model [mouse]
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.1 ST Array (mogene21st)

Description

CaSR modulation inhibits neuroblastoma growth

Publication Title

Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE73504
CaSR modulator in neuroblastoma model [human]
  • organism-icon Homo sapiens
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Human Gene 2.1 ST Array (hugene21st)

Description

CaSR modulation inhibits neuroblastoma growth

Publication Title

Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.

Sample Metadata Fields

Specimen part, Treatment

View Samples
accession-icon GSE62251
Inhibition of the autocrine loop IL6-JAK2-STAT3-Calprotectin as targeted therapy for HR-/HER2+ breast cancers
  • organism-icon Homo sapiens
  • sample-icon 21 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V3.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers.

Sample Metadata Fields

Cell line

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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