Whether the human tumor virus, Epstein-Barr virus (EBV) promotes breast cancers remains controversial and a potential mechanism has remained elusive. Here we show EBV can infect primary mammary epithelial cells (MECs) that express the attachment receptor, CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, including expression of latent membrane proteins 1 (LMP1) and 2 (LMP2), similar to nasopharyngeal carcinoma (NPC). A human gene expression signature for EBVness was generated based on the RNA expression profile of the EBV infected primary mammary epithelial cells, tumors. This was signature associated with high grade (40 vs 13.5%) estrogen-receptor-negative status (31.8 vs. 10.5%, p53 mutation (37.5 vs 14.5%) and poor survival. In 11/33 (33%) of tumors positive for EBVness EBV-DNA was found in tumor cells by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes, while only 4/36 (11%) of EBVness-negative tumors tested positive for EBV DNA. An analysis of the TCGA breast cancer data revealed a correlation of EBVness with presence of the APOBEC mutational signatures consistent with past viral infection. We conclude that a contribution of EBV to breast cancer etiology via a hit-and-run mechanism is plausible, in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is not required for the maintenance of the malignant phenotype.
Epstein-Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation.
Specimen part, Cell line
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Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs.
Specimen part, Treatment
View SamplesWe report the in vivo androgen receptor (AR) binding sites in murine prostate, epididymis and kidney in response to physiological androgen testosterone using ChIP-sequencing and gene expression profiling by microarray. From AR cistrome analysis, we identified tissue-specific collaborating factors i.e. FoxA1 in prostate, Hnf4a in kidney and AP2a in epididymis and validated by ChIP-seq. The ChIP experiments have been performed using antibodies specific to AR, FoxA1, Hnf4a, AP-2a and IgG non-specific antibody as a negative control.
Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs.
Specimen part
View SamplesWe report that the phytoestrogen genistein acts as a tissue-specific androgen receptor modulator in mouse using a novel androgen reporter mouse line and gene expression profiling. Genistein is a partial androgen agonist/antagonist in prostate, brain, and testis but not in skeletal muscle or lung. Gene expression profiling has been done from prostates of intact and castrated male mice treated with genistein or vehicle. Gene expression profiling was also done from prostates of estradiol-treated intact male mice.
The phytoestrogen genistein is a tissue-specific androgen receptor modulator.
Sex, Specimen part
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FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells.
Specimen part, Cell line, Treatment
View SamplesWe report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate and mifepristone (RU486) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies.
FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells.
Cell line, Treatment
View SamplesHepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2), we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays.
Thyroid hormone-related regulation of gene expression in human fatty liver.
Sex, Age
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EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.
Specimen part, Cell line
View SamplesThe incidence of keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC) is increasing worldwide making it the second most common metastatic skin cancer.
EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.
Specimen part, Cell line
View SamplesThe role of Eph/ephrin signaling in numerous biological processes has been established. However, Eph/ephrin signaling has been shown to have complex role in tumor progression. The role of EphB2 receptor in the progression of cutaneous squamous cell carcinoma (cSCC) has not been studied before.
EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.
Cell line
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