Prostate cancer (PC) is initially dependent on androgen receptor (AR) signaling for survival and growth. Therapeutics designed to repress AR activity, such as those reducing circulating androgen levels, serve as the primary intervention for advanced disease. However, supraphysiological androgen (SPA) concentrations, can produce a paradoxical response leading to growth inhibition. We sought to determine the mechanisms by which SPA represses PC growth and determine if molecular context associates with anti-tumor effects. Overall design: RNA sequencing of LNCaP human prostate tumor cell lines using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.
Supraphysiological androgens suppress prostate cancer growth through androgen receptor-mediated DNA damage.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesAndrogen receptor (AR) signaling is a distinctive feature of prostate cancer (PC) and represents the major therapeutic target for the treatment of metastatic disease. Though highly effective, AR antagonism has the potential to generate tumors that bypass a functional requirement for AR activity. We show here that a phenotypic shift has occurred in metastatic PCs with the emer-gence of a double-negative AR-null neuroendocrine-null phenotype that is notable for MAPK and FGF pathway activity. To identify mechanisms capable of sustaining PC survival, we gener-ated a model system designated AR program-independent prostate cancer (APIPC) which re-sists AR-targeted therapeutics, lacks neuroendocrine features, expresses high levels of FGF8 and the ID1 oncogene, and activates MAPK signaling. Pharmacological blockade of MAPK or FGF signaling inhibited APIPC tumor growth, supporting FGF/MAPK as a therapeutic avenue for treating AR-null PC. Overall design: RNA sequencing of human prostate tumor cell lines using the Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.
Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling.
Sex, Specimen part, Cell line, Subject
View SamplesA total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR < 0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR < 0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated.
A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.
Disease, Disease stage
View SamplesTwo-week old rice plants (cultivar Nipponbare) were treated with either Magnaporthe grisea (virulent isolate FR13) spore suspension in gelatine or gelatine alone. Two time points were taken (3 and 4 days post inoculation- dpi). Disease symptoms were not visible at 3 dpi whereas they were at 4 dpi. Two biological repeats were done.
Susceptibility of rice to the blast fungus, Magnaporthe grisea.
No sample metadata fields
View SamplesThe estrous cycles of Limousin heifers (n = 30) were synchronized by insertion of a controlled internal drug release (CIDR) device (1.94 g progesterone; Pfizer Animal Health) placed into the vagina for 8 days. A 0.5 mg intramuscular injection of a prostaglandin F2a (PG) analogue (PG, Estrumate, Shering-Plough Animal Health, Hertfordshire, UK) was administered 1 day before CIDR removal. Heifers were checked for standing estrus and only those exhibiting estrus (Day 0) were used. All animals were expected to come in heat between 48 and 72 hours after CIDR removal. Cervical tissues were collected at slaughter from heifers 12h after CIDR removal (Group 1: CIDR + 12 h, n = 6), 24h after CIDR removal (Group 2: CIDR + 24 h, n = 6), at the onset of estrus (Group 3: Estrus, n = 4), 12 h after the onset of estrus (Group 4: estrus + 12 h, n = 5), 48 h after the onset of estrus (Group 5: Estrus+48h, n = 4) and on day 7 after the onset of estrus (Group 6: Luteal phase, n = 5). Overall design: Cervical tissue from 30 animals taken at 6 timepoints in the peri-oestrus period. +12hrs post CIDR, Onset of Oestrus,+12hrs post Oestrus, +48hrs post Oestrus, Luteal phase
Molecular aspects of mucin biosynthesis and mucus formation in the bovine cervix during the periestrous period.
Subject, Time
View SamplesWe have identified a CD57+PD1- CD4 T cell phenotype at the time of transplantation that strongly correlates with subsequesnt development of belatacept-resistant rejection. In this study, we used microarray to determine which genes were upregulated in CD57+ compared to CD57- CD4 T cells.
CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.
Specimen part, Subject
View SamplesCD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is not clear how SIV infection is controlled in germinal center during chronic SIV infection and limited information exists on the characteristics of CXCR5+ CD8 T cells during chronic SIV/HIV infection. In this study, we used functional genomics to investigate characteristic features and potential mechanisms of CXCR5+ and CXCR5- SIV specific CD8 T cells for the control of pathogenic SIV infection. Six chronically SIV infected RMs, three SIVE660 infected and three SIV mac251 infected that are positive for Mamu A01 allele were selected and SIV-specific CXCR5+ and CXCR5- CD8 T cells were sorted based on CXCR5 expression. RNA from sorted cells were extracted and microarray were performed and analysed. Principal component analysis demonstrated that overall gene expression difference between CXCR5+ and CXCR5- SIV-specific CD8 T cells. Interestingly, the CXCR5+ CD8 T cells revealed a distinct gene signature pattern when compared to CXCR5- CD8 T cells. Unlike the CXCR5- CD8 T cells, the CXCR5+ CD8 T cells expressed higher levels of genes associated with Tfh CD4 T cells such as the master transcription factor Bcl6, CD200, and CTLA4 as well as markers associated with Th2 CD4 T cells such as IL-4R (CD124), CCR4, STAT6, NFATC, and IL-10. Effector molecules typically observed in cytotoxic CD8 T cells such as granzyme A, B, and K were expressed at lower levels on CXCR5+ CD8 T cells compared to their CXCR5- counterparts. CXCR5+ CD8 T cells also expressed higher levels of molecules associated with co-stimulation/antigen presentation such as CD40, CD83, 41BBL and MAMU-DRA. The CXCR5+ CD8 also expressed higher levels of inhibitory receptors such as CD200 and SPRY2 but lower levels of other inhibitory receptors CD160 and CD244. The functional consequence of the expression of these molecules is yet to be determined. Additionally, CXCR5+ CD8 T cells expressed higher levels of the anti-apoptotic gene Bcl-2 and lower levels of the pro-apoptotic gene annexin, suggestive of their better survival potential during chronic SIV infection. Collectively, these results demonstrate that SIV specific CXCR5+ CD8 T cells possess a unique gene expression signature compared to SIV-specific CXCR5- CD8 T cells.
Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
Specimen part, Disease, Disease stage
View SamplesWe used microarray to compare gene expression between CD161++/CD161+/CD161-CD8+ T cells from human cord blood.
Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
Specimen part
View SamplesWe used microarrays to compare gene expression between healthy human CD161++CD8aa and CD161++CD8ab T cells.
Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
Specimen part, Disease, Disease stage
View Samples