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Homo sapiens
55 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ovarian clear cell carcinoma (CCC) is generally associated with chemoresistance and poor clinical outcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs) and endometrioid carcinomas (ECs) are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism arrays in 57 (31 CCCs, 14 SCs, and 12 ECs) and expression microarrays in 55 epithelial ovarian cancers (25 CCCs, 16 SCs, and 14 ECs), and then evaluated PIK3CA mutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs), significantly lower than for SCs (93%, P < 0.01) and ECs (50%, P = 0.017). The ratio of whole-arm to all CNAs was higher in CCCs (46.9%) than SCs (21.7%) (P < 0.0001). SCs with loss of heterozygosity (LOH) of BRCA1 (85%) also had LOH of NF1 and TP53, and LOH of BRCA2 (62%) coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10) showed more favorable prognosis than the others (CCC-1and CCC-3) (P = 0.041). Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64%) than in CCC-2 (0/10, 0%) (P < 0.01). Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis.
Publication Title
Correction: Integrated Copy Number and Expression Analysis Identifies Profiles of Whole-Arm Chromosomal Alterations and Subgroups with Favorable Outcome in Ovarian Clear Cell Carcinomas.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Evi1 is essential for proliferation of hematopoietic stem cells and implicated in the development of myeloid disorders. Particularly, high Evi1 expression defines one of the largest clusters in acute myeloid leukemia and is significantly associated with extremely poor prognosis. Improvement of the therapeutic outcome of leukemia with activated Evi1 is one of the most challenging issues. However, mechanistic basis of Evi1-mediated leukemogenesis has not been fully elucidated. Here we show that Evi1 directly represses PTEN transcription in the murine bone marrow, which leads to activation of AKT/mTOR signaling. In a murine bone marrow transplantation model, Evi1 leukemia showed remarkable sensitivity to an mTOR inihibitor rapamycin. Furthermore, we found that Evi1 binds to several polycomb group proteins and recruits polycomb repressive complexes for PTEN downregulation, which reveals a novel epigenetic mechanism of AKT/mTOR activation in leukemia. Expression analyses and chromatin immunoprecipitation assays using human samples indicate that our findings in mice models are recapitulated in human leukemic cells. Dependence of Evi1-expressing leukemic cells on AKT/mTOR signaling provides the first example of targeted therapeutic modalities that suppress the leukemogenic activity of Evi1. The PTEN/AKT/mTOR signaling pathway and the Evi1-polycomb interaction can be promising therapeutic targets for leukemia with activated Evi1.
Publication Title
Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Aberrant activation of Wnt beta-catenin signalling is a major driving force in colon cancer. Wnt beta-catenin signalling induces the expression of the transcription factor c-Myc, leading to cell proliferation and tumourigenesis. c-Myc regulates multiple biological processes through its ability to directly modulate gene expression. However, the mechanisms underlying c-Myc-induced oncogenesis remain to be established. Here we identify a novel direct target of c-Myc, MYU (c-Myc-upregulated long non-coding RNA) and show that MYU is upregulated in most colon cancers and is required for the tumourigenicity of colon cancer cells. We further demonstrate that MYU associates with the RNA-binding protein hnRNP-K to stabilize CDK6 expression, and thereby promotes the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signalling and plays a critical role in the proliferation and tumourigenicity of colon cancer cells. MYU might be a promising molecular target for the therapeutic treatment of c-Myc-driven cancers.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples
GSE62319- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify the target genes of Evi-1 in hematopoietic stem cells (HSCs), we carried out genome-wide transcriptional analysis using wild-type and Evi-1-deleted HSCs.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To investigate genes possibly regulated by TTF-1 in small cell lung cancer cell lines, we compared gene expression profiles of NCI-H209 and Lu139 cell lines electroporated with control and TTF-1 siRNAs.
Publication Title
An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To investigate the roles of TAZ in lung cancer cell proliferation, we compared the expression profiles of A549 and H441 lung adenocarcinoma cell lines transfected with control siRNA and siTAZ.
Publication Title
An integrative analysis of the tumorigenic role of TAZ in human non-small cell lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells. Anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for maintaining the stem-like properties and tumorigenicity of glioblastoma stem cells.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
GATA6 is a zinc finger transcription factor that is required for the proliferation, development and specific gene regulation in the gastrointestinal tract. We have recently reported that GATA6-mediated induction of the intestinal stem cell marker LGR5 is required for the tumorigenicity of colon cancer cells. However, knockdown of LGR5, unlike GATA6, does not affect the proliferation of these cells under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is a target of GATA6. We further demonstrate that REG4 is downregulated by overexpression of miR-363, which suppresses GATA6 expression. Moreover, we show that GATA6-mediated activation of REG4 causes an acceleration of the growth of colon cancer cells under adherent conditions. These results suggest that GATA6 simultaneously activates the transcription of genes required for growth (REG4) and clonogenicity (LGR5), and the miR-363-GATA6-REG4/LGR5 pathway is critical for colorectal tumorigenesis.
Publication Title
REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
GATA6 is a zinc finger transcription factor that is required for the proliferation, development and specific gene regulation in the gastrointestinal tract. We have recently reported that GATA6-mediated induction of the intestinal stem cell marker LGR5 is required for the tumorigenicity of colon cancer cells. However, knockdown of LGR5, unlike GATA6, does not affect the proliferation of these cells under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is a target of GATA6. We further demonstrate that REG4 is downregulated by overexpression of miR-363, which suppresses GATA6 expression. Moreover, we show that GATA6-mediated activation of REG4 causes an acceleration of the growth of colon cancer cells under adherent conditions. These results suggest that GATA6 simultaneously activates the transcription of genes required for growth (REG4) and clonogenicity (LGR5), and the miR-363-GATA6-REG4/LGR5 pathway is critical for colorectal tumorigenesis.
Publication Title
REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples