The cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor).
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα- breast cancer.
Specimen part
View SamplesTo model the effect of Pten loss on breast cancer, we deleted Pten using a floxed allele and the deleter lines MMTV-Cre(NLST), which targets stem/bi-potent progenitor cells, and WAP-Cre, which targets CD24-positive, pregnancy-identified stem cells/alveolar progenitors. Mammary tumors were detected in WAP-Cre:Ptenf/f females with a latency of 15.2 months. By 18 months, nearly all mice had succumbed to cancer. MMTV-Cre:Ptenf/f mice developed mammary tumors after a longer latency of 26.4 months and reduced penetrance (70%) compared to WAP-Cre:Ptenf/f mice. Tumors from both models were heterogeneous, consisting primarily of differentiated adenocarcinoma (adenomyoepithelioma; ~70%) and adenosquamous carcinoma (20-25%). In addition, a small fraction of tumors was classified as acinar and poorly differentiated adenocarcinoma (4-7%) and adenosarcoma (3-4%). To test the consequences of combined Pten and p53 gene mutation on breast cancer, we deleted both genes via MMTV-Cre or WAP-Cre. Kaplan-Meier tumor free survival curves revealed that WAP-Cre:Ptenf/f:p53f/f and MMTV-Cre:Ptenf/f:p53f/f females developed tumors with reduced latency of 11.3 and 9.8 months, compared with 15.2, 26.4, and 16.9 months for single-mutant WAP-Cre:Ptenf/f, MMTV-Cre:Ptenf/f or MMTV-Cre:p53f/f mice, respectively. In contrast to the heterogeneity of Pten tumors and small percentage of adenosarcomas in these mice, ~70% of Pten:p53 lesions were histologically classified as adeno-sacrcomatoid-like or mesenchymal-like breast cancer, with the rest exhibiting mixed mesenchymal plus adenocarcinomas and differentiated adenocarcinomas. The adeno-sacrcomatoid-like tumors expressed the mesenchymal markers vimentin, K5, SMA, N-cadherin and desmin but not ER, as well as islands of luminal-like K18 expressing cells surrounded by a layer of K14-positive cells.
Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways.
Specimen part, Cell line, Treatment
View SamplesWe studied the effect of knowking down SUZ12 +/- knowckdown of BRM on the responsivness of IFNg stimulated genes. Cells were transfected with siSZU12+/-siBRM or control siRNA+/-siBRM. Cells were then left untreated or exposed to IFNg for 6 hours.
Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways.
Cell line
View SamplesWe studied the effect of reconstitution of BRG1 in BRG1-deficient cells on the responsivness of IFNg stimulated genes. Cells were infected with control adenovirus or BRG1-encoding virus. Cells were then left untreated or exposed to IFNg for 6 hours.
Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways.
Cell line
View SamplesMicroarray analysis was performed at the UHN Microarray Centre (UHNMAC, Ontario, Canada) using Illumina HumanHT-12 v4 BeadChip with 500 ng of total RNA prepared by RNeasy mini kit (QIAGEN, Cat. No. 74104). Samples from HCC1954 cells with 3-day treatment of TBK1-II at 4 uM were used to compare with vehicle-treated controls. Microarray data was processed and normalized by lumi package from BioConductor in R with Quantile Method. Difference between the samples were calculated by Bayesian statistic using limma package from BioConductor in R to obtain Moderated T value for subsequent Pathway analysis.
shRNA kinome screen identifies TBK1 as a therapeutic target for HER2+ breast cancer.
Cell line
View SamplesBreast Cancer (BC) has been associated with alterations in signaling through a number of growth factor and hormone regulated pathways. Mouse models for metastatic BC have been developed using oncoproteins that activate PI3K, Stat3 and Ras signaling. To determine the role of each pathway, we analyzed mouse mammary tumor formation when they were activated singly or pairwise.
Ras Signaling Is a Key Determinant for Metastatic Dissemination and Poor Survival of Luminal Breast Cancer Patients.
Specimen part
View SamplesThis study examines the sites of HIV integration in quiescent CD4 T cells and compares them to activated T cells. The expression patterns of the sites hosting integration events were determined using microarray analysis data from quiescent and activated CD4 T cells.
Human immunodeficiency virus integration efficiency and site selection in quiescent CD4+ T cells.
No sample metadata fields
View SamplesWe examined the efffects of ligating CD4 expressed by primary human peripheral blood monocytes with soluble MHC Class II.
CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection.
Specimen part, Treatment
View SamplesKSHV RTA (K-RTA) is a transcriptional activator that functions to disrupt KSHV latency and activates specific sets of viral promoters in the lytic cycle. Structure-function studies indicate that K-RTA possesses a very potent transactivation domain locating at the C-terminus. To further characterize the biological functions of K-RTA, we have established three doxycycline-inducible K-RTA 293 cell lines using RevTRE/Tet-On system (Clontech). Comparing to two control lines in which K-RTA was replaced with luciferase reporter, a total of 88 host genes were identified to be modulated by 24 h doxycycline-induced K-RTA synthesized in 293 cells.
Gene expression and transcription factor profiling reveal inhibition of transcription factor cAMP-response element-binding protein by gamma-herpesvirus replication and transcription activator.
Specimen part, Cell line
View Samples