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RNA Expression Data from IL-15-/- and IL-15+/+ TAX-LUC Mouse Tumors

ABSTRACT: IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia / lymphoma (ATL) and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma. We used microarrays to compare the gene expression profile of tumors in IL-15-/- TAX-LUC mice to IL-15+/+ TAX-LUC mice RNA was obtained from CD16/32HI and CD16/32LO cells harvested from n=2 IL-15+/+ (control)and n=2 IL-15-/- Tax tumors and was compared to look for alterations in gene expression in malignant and tumor infiltrating cells resulting from loss of IL-15 in vivo

ORGANISM(S): Mus musculus

SUBMITTER: Rekha Meyer

PROVIDER: E-GEOD-46072 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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RNA Expression Data from IL-15-/- and IL-15+/+ TAX-LUC Mouse Tumors

Project description:IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia / lymphoma (ATL) and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma. We used microarrays to compare the gene expression profile of tumors in IL-15-/- TAX-LUC mice to IL-15+/+ TAX-LUC mice

2013-06-11 | GSE46072 | GEO

Mus musculus

Project description:RNA Expression Data from IL-15-/- and IL-15+/+ TAX-LUC Mouse Tumors

| PRJNA197152 | ENA

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (LYM1, KK1).

Project description:Adult T-cell leukaemia-lymphoma (ATL) is a highly chemoresistant malignancy of peripheral T lymphocytes caused by human T-lymphotropic virus type I (HTLV-1). ATL cells constitutively activate anti-apoptotic signals through nuclear factor kappaB (NF-κB)-mediated gene expression. The molecular chaperon heat shock protein 90 (HSP90) plays a crucial role on NF-κB-mediated anti-apoptotic activity in ATL cells and HSP90 inhibitors, such as 17-DMAG and NVP-AUY922, have demonstrated their anti-ATL activities. A novel class of orally active inhibitors of cytosolic HSP90α and β, pimitespib, demonstrated its highly selective anti-ATL cell effects both ex-vivo and in vivo preclinical models. Ten ATL-related cell lines achieved their IC50 below 0.5µM dose of TAS-116 while CD4 lymphocytes derived from healthy donors were less harmed than ATL cells. TAS-116 efficiently induces Tax-degradation and IκB-α accumulation to Tax-positive cell-lines. DNA microarray profiling followed by a variety of pathway analysis revealed that TAS-116 down-regulated NF-κB activating pathways in Tax-positive cells and cell cycle promoting pathways in Tax-negative cells and induces anti-ATL effect. Oral administration of TAS-116 to ATL-cell xenograft model mice also demonstrated the growth inhibitory effects against tumor cells. Consequently, TAS-116, one of the most evolved HSP90 inhibitor, may become a promising option against ATL therapy.

2022-02-18 | GSE168555 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (HuT102).

2022-02-18 | GSE168554 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (ED).

2022-02-18 | GSE168552 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Su9T01).

2022-02-18 | GSE168558 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Pt1-3).

2022-02-18 | GSE168557 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (OATL4).

2022-02-18 | GSE168556 | GEO

Transcription profiling of human CD4+ T-cell line Tesi in presence and absence of Tax

Project description:The Tesi system allows analysis of HTLV-1 Tax's impact on the transcriptome of a human CD4+ T-cell which is not derived from leukemia but directly from normal human lymphocytes. By comparing cells with and without Tax, one can specifically filter for celluar genes that are either activated or repressed in the presence of Tax. Experiment Overall Design: Tesi cells were kept in RPMI 1640 with 50% Panserin, 20% FCS, 0.35g/l glutamine, streptomycin as antibiotic and 40U/ml interleukin-2. To repress Tax expression, 1Âµg/ml tetracycline was added for ten days. Subsequently, total cellular RNA was extracted from samples and subjected to Affymetrix microarray analysis. For each state (with Tax and without Tax) a biological replicate was generated. Mean values of replicated samples were then compared.

2008-04-07 | E-GEOD-10508 | biostudies-arrayexpress

Profile of gene expression in Tax positive (TaxP) cells compared with Tax negative (TaxN) cells.

Project description:Investigating the effect of Tax protein on the expression of genes in Jurkat cells. Current study will help us to elucidate the differential gene expression profiles of Tax positive Jurkat cells. The Tax-positive (TaxP) and Tax negative (TaxN) subline of Jurkat were established. mRNA isolated from TaxN or TaxP cell lines were analyzed using gene array.

2012-07-26 | E-GEOD-39601 | biostudies-arrayexpress

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