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SRP170415
Homo sapiens
8 Downloadable Samples
Illumina HiSeq 2500
Description
Heterozygous mutations in the transcription factor GATA3 are identified in 10-15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expression and promotes anchorage-independent growth in vitro. However, we could not identify any effects of truncated GATA3 expression on mammary gland development or mammary tumor formation in mice. Together, our results demonstrate that both truncated GATA3 mutants promote cistromic re-programming of GATA3 in vitro, but these mutants are not sufficient to induce tumor formation in mice. Overall design: RNAseq data of T47D cells expressing HA-tagged wild-type GATA3 (HA_GATA3_wt) or one of two truncated variants (HA_GATA3_TR1 and HA_GATA3_TR2).
Publication Title
GATA3 Truncating Mutations Promote Cistromic Re-Programming In Vitro, but Not Mammary Tumor Formation in Mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer.
Publication Title
Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 110 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of 104 breast cancer biopsies (removed prior to any treatment with tamoxifen or chemotherapeutic agents) from patients aged between 31 years and 89 years at the time of diagnosis (mean age = 58 years). Twenty were less than 50 years and seventy-seven women were 50 years, or older, at diagnosis. The size of the tumours ranged between 0.6 cm and 8.0 cm (mean = 2.79 cm). Eighteen tumours were T1 (<2 cm) in maximal dimension; 83 were T2 (25 cm) and 3 tumours were T3 (>5 cm). Eighty-two were invasive ductal carcinoma, 17 were invasive lobular and five were tumours of special type (two tubular and three mucinous). Eleven tumours were grade 1; 40 were grade 2; and 53 were grade 3. Sixty-seven tumours were oestrogen receptor (ER) positive and 34 were ER negative (ER status was determined by Enzyme Immuno-Assay (EIA); a positive result was defined as more than 200 fmol/g protein). ER status was not available for 3 patients. Forty-five tumours had no axillary metastases and 59 tumours had metastasised to axillary lymph nodes. Sixty-nine women were treated with post-operative tamoxifen; 26 did not receive tamoxifen. Fifty patients were treated with adjuvant systemic chemotherapy (CMF +/ adriamycin); 45 patients did not receive chemotherapy. Details regarding tamoxifen and systemic chemotherapy were not available for 9 patients. Maximal follow-up was 3,026 days with a mean follow-up of 1,887 days.
Publication Title
Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis.
Sample Metadata Fields
Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 68 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Homologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities. Here, we identified an HRD gene signature that robustly predicted HRD status. Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK. We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map. Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information.
Publication Title
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Homologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities. Here, we identified an HRD gene signature that robustly predicted HRD status. Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK. We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map. Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information.
Publication Title
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Homologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities Here, we identified an HRD gene signature that robustly predicted HRD status Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information
Publication Title
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Macaca mulatta
- 21 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
This study was designed to provide a genome-wide analysis of the effects of luteinizing hormone (LH) ablation/replacement versus steroid ablation/replacement on gene expression in the developed corpus luteum (CL) in primates during the menstrual cycle. Naturally cycling, female rhesus monkeys were left untreated (Control; n = 4) or received one of the following treatments for three days beginning on Day 9 of the luteal phase: daily injection of the gonadotropin-releasing hormone (GnRH) antagonist (Antide; n = 5), Antide + recombinant human LH (A+LH; n = 4), Antide + LH + the 3b-HSD antagonist Trilostane (A+LH+TRL; n = 4), and Antide + LH + TRL + progesterone replacement with a synthetic progestin R5020 (A+LH+TRL+ R5020; n = 5). On Day 12 of the luteal phase, CL were removed and samples of RNA from individual CL were fluorescently labeled and hybridized to Affymetrix rhesus macaque total genome microarrays. The greatest number of altered transcripts was associated with the ablation/replacement of LH, while ablation/replacement of progestin affected fewer transcripts. Replacement of LH during Antide treatment restored expression of most transcripts to control levels. Real-time PCR validation of a subset of transcripts revealed that most expression patterns were similar between microarray and real-time PCR. Analysis of protein levels were subsequently determined for 2 of the transcripts differentially expressed by real-time PCR. This is the first genome-wide analysis of LH and steroid regulation of gene transcription in the developed primate CL. Further analysis of novel transcripts identified in this data set can clarify the relative role for LH and steroids in CL maintenance and luteolysis.
Publication Title
The effects of luteinizing hormone ablation/replacement versus steroid ablation/replacement on gene expression in the primate corpus luteum.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta
- 12 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Luteolysis of the corpus luteum (CL) during non-fertile cycles involves a cessation of progesterone (P4) synthesis (functional regression) and subsequent structural remodeling. The molecular processes responsible for initiation of luteal regression in the primate CL are poorly defined. Therefore, a genomic approach was utilized to systematically identify differentially expressed genes in the rhesus macaque CL during spontaneous luteolysis. CL were collected prior to (days 10-11 post-LH surge, mid-late [ML] stage) or during (days 14-16, late stage) functional regression. Based on P4 levels, late stage CL were subdivided into functional late (FL, serum P4 > 1.5 ng/ml) and functionally-regressed late (FRL, serum P4 < 0.5 ng/ml) groups (n=4 CL/group). Total RNA was isolated, labeled and hybridized to Affymetrix genome microarrays that contain elements representing the entire rhesus macaque transcriptome. With the ML stage serving as the baseline, there were 681 differentially expressed transcripts (>2-fold change; p< 0.05) that could be categorized into three primary patterns of expression: 1) increasing from ML through FRL, 2) decreasing from ML through FRL, and 3) increasing ML to FL, followed by a decrease in FRL. Ontology analysis revealed potential mechanisms and pathways associated with functional and/or structural regression of the macaque CL. Quantitative real-time PCR was used to validate microarray expression patterns of 13 genes with the results being consistent between the two methodologies. Protein levels were found to parallel mRNA profiles in 4 of 5 differentially expressed genes analyzed by Western blot. Thus, this database will facilitate the identification of mechanisms involved in primate luteal regression.
Publication Title
Dynamic changes in gene expression that occur during the period of spontaneous functional regression in the rhesus macaque corpus luteum.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mammary epithelial cells MCF10A and HER2 overexpressing MCF10A cells were grown on matrigel in the absence or presence of epidermal growth factor. Cells were lysed and RNA was collected at 1.5,3,5,7,9 days.
Publication Title
Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling.
Sample Metadata Fields
Cell line, Treatment
View Samples