Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression.
Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia.
Specimen part, Subject
View SamplesBreast cancer is a highly heterogeneous disease that is categorized into distinct tumor subtypes based on specific molecular attributes, which ultimately influence therapeutic options. Unlike ER+ and/or HER2+ cancers that are subject to specific targeted therapies, triple negative breast cancers (TNBCs) do not express these receptors, which leaves patients with limited treatment options. Thus, significant focus has been placed on identifying molecular attributes of basal-like disease that could be used to develop and/or direct novel treatment regimens. Activation of MYC signaling and inactivation of the RB-pathway are frequent events in many types of human cancers. These pathways influence many biological processes, such as cell proliferation, that contribute to the aggressiveness and therapeutic response of tumors. The current study examines the interaction of the MYC and RB pathways in mammary epithelial cell tumorigenesis.
RB loss contributes to aggressive tumor phenotypes in MYC-driven triple negative breast cancer.
Sex, Age, Specimen part
View SamplesThe LXCXE peptide motif facilitates interaction between the RB tumor suppressor and a large number of cellular proteins that are expected to impinge on diverse biological processes. In vitro and in vivo analyses demonstrated that LXCXE-binding function is dispensable for RB promoter association and control of basal gene expression. Dependence on this function of RB is unmasked after DNA damage, wherein LXCXE-binding is essential for exerting control over E2F3 and suppressing cell cycle progression in the presence of genotoxic stress. Gene expression profiling revealed that the transcriptional program coordinated by this specific aspect of RB is associated with progression of human hepatocellular carcinoma and poor disease outcome. Consistent with these findings, biological challenge revealed a requirement for LXCXE-binding in suppression of genotoxin-initiated hepatocellular carcinoma in vivo. Together, these studies establish an essential role of the LXCXE-binding motif for RB-mediated transcriptional control, response to genotoxic insult, and tumor suppression.
RB restricts DNA damage-initiated tumorigenesis through an LXCXE-dependent mechanism of transcriptional control.
Treatment
View SamplesProstate cancer is dependent on androgen receptor (AR) signaling at all stages of the disease and cyclin D1 has been shown to negatively modulate the expression of the AR-dependent gene prostate specific antigen (KLK3/PSA).
Cyclin D1 is a selective modifier of androgen-dependent signaling and androgen receptor function.
Cell line, Treatment
View SamplesBAF57, a component of the SWI/SNF chromatin remodeling complex conglomerate,modulates androgen receptor activity to promote prostate cancer. However the molecular consequences of tumor associated BAF57 elevation have remianed undefined in advanced disease such as castration resistant prostate cancer and/or metastasis
Aberrant BAF57 signaling facilitates prometastatic phenotypes.
Specimen part, Treatment
View SamplesCpG 1826 binds to Toll-like receptor (TLR)9, whereas influenza virus PR8 activates pDC via TLR7. Differential stimulation of pDCs is expected to result in unique activation mechanism(s) leading to a different phenotypically and functionally matured pDC
Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide.
No sample metadata fields
View SamplesAfter induction of ischemic chronic heart failure (CHF), mice exhibited depression-like behavior, in terms of increased anhedonia, and decreased both exploratory activity and interest in novelty. On histology, ischemic CHF mice showed no alterations in overall cerebral morphology. To further evaluate relevant behavioral changes found in CHF mice, RNA-sequencing analysis of prefrontal cortex and hippocampus - the brain regions, whose structural and functional alterations are associated with an increased risk for developing major depressive disorder - and of left myocardial tissue was performed in CHF vs. sham-operated animals. RNA-sequencing revealed relevant changes in hippocampal or prefrontal cortical expression of genes responsible for axonal vesicle transport (Kif5b), signal transduction (Arc, Gabrb2), limitation of inflammation (RORA; Nr4a1) and of hypoxic brain damage (Hif3a). Besides, the actual literature describes some of the genes (RORA, Gabrb2, Npas4, and Junb) being associated with depression-like behavior. Nr4a1 significantly regulated in both brain and heart tissue after induction of ischemic CHF could be a potential link and reveals the central role of inflammation in the interrelation of the brain and the failing heart. Overall design: Heart failure vs. sham-operation were performed in C57BL/6 male mice. After development of chronic heart failure (CHF) 8 weeks after the operation RNA was extracted out of prefrontal cortex, hippocampus and left ventricular myocardium in both groups. RNA of 3 ischemic CHF mice versus 6 sham operated mice was pooled and further subjected to RNA sequencing. To fabricate singular pools each probe of the group equally contributed with the final amount of 2 µg RNA per pool with the result that we had 6 different pools to be further evaluated. The mRNA profile was generated by IGA Technology, Italy (http://www.igatechnology.com/) by deep sequencing, using Illumina HiSeq 2000 platform (HiSeq). CLC-Bio Genomics Workbench software (CLC Bio, Denmark) was used to calculate gene expression levels based on Mortazavi et al. (Nat Methods. 2008;5:621-628) approach.
Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain.
No sample metadata fields
View SamplesAnalysis of mammary glands from tet-inducible (rtTA) transgenic mice expressing cyclin D1 (Ccnd1). MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under the control of the tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and were treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction.
ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice.
Specimen part
View SamplesTranscriptome analysis of a population of wild type animals and lsm-1 mutants at L3 stage Overall design: lsm-1(tm3585) mutants were backcrossed three times with wild type N2 animals. lsm-1 mutants and N2 animals were grown for 26 hours at 25C from a synchronized L1 population.
Cytoplasmic LSM-1 protein regulates stress responses through the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell cycle-coupled expansion of AR activity promotes cancer progression.
Cell line
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