Project description:PTEN is one of the most altered tumor suppressor genes in human prostate cancer. Prostate specific-Pten-deficient mouse models develop prostate cancer eventually progressing to CRPC, also due to alterations of the tumor immune infiltrate.
Project description:Gene expression data from Agilent-014850 4x44K human expression array for CRPC Prostate Cancer study with Xenograph data. RNA was isolated using the mirVana total RNA protocol (part #AM1560, Ambion, Austin, TX). RNA integrity was verified using a 2100 Bioanalyzer (part #G2938A) with nano chips (parts #5067-15101 and #G4411B; Agilent Technologies, Alto, CA). RNA concentrations were determined using a Nanodrop spectrophotometer (Thermo Scientific, Wilmington, DE). Tumor messenger RNA expression was assessed using a human whole-genome oligo TMA kit from Agilent (prod #G4112F) according to the manufacturer’s protocol and as described previously. In the Characteristics field, we have the notation like "Pt Dxed in 2001; hormone Tx; chemo Tx 2002; HRPC by 2002". That means the patient was admitted in 2001, did hormone and chemo treatment in 2002, and HRPC 2002. They are standard prostate cancer treatments.
Project description:Our understanding of cell fate decisions in hematopoietic stem cells is incomplete. Here, we show that the transcription factor Helios is highly expressed in murine hematopoietic stem and progenitor cells (HSPCs), where it is required to suppress the separation of the platelet/megakaryocyte lineage from the HSPC pool. Helios acts mainly in quiescent cells, where it directly represses the megakaryocyte gene expression program in cells as early as the stem cell stage. Helios binding promotes chromatin compaction, notably at the regulatory regions of platelet-specific genes recognized by the Gata2 and Runx1 transcriptional activators, implicated in megakaryocyte priming. Helios null HSPCs are biased toward the megakaryocyte lineage at the expense of the lymphoid and partially resemble cells of aging animals. We propose that Helios acts as a guardian of HSPC pluripotency by continuously repressing the megakaryocyte fate, which in turn allows downstream lymphoid priming to take place. These results highlight the importance of negative and positive priming events in lineage commitment.
Project description:Our studies revealed a novel oncogenic function of LSD1 in driving PCa progression by activating MYC signaling and mediating CRPC SEs activities, cotargeting LSD1 and BRD4 achieved significant synergistic effects in repressing CRPC tumor growth
Project description:Identifying biological change from hormone-naive prostate cancer to CRPC is a major clinical challenge for developing therapeutic agents. Although the pathways that lead to CRPC are not fully understood, recent evidence demonstrates that androgen signaling is often maintained through varied mechanisms. Here, we investigated PCa tissues at each stage of progression from benign prostatic hyperplasia (BPH) to CRPC based on quantitative proteomic technology, including tissues after ADT therapy. MS-based quantitative proteomics approach based on 6-plex TMT (126-131) was performed in patient tissues from T2G2 to CRPC, and benign prostatic hyperplasia (BPH) patient tissues were used as a control. We analyzed the peptide samples using two types of high resolution and accuracy mass spectrometers as LTQ orbitrap velos and Q-exactive mass spectrometer. In total, 4,768 proteins were identified in this study, among which 4,069 proteins were quantified in the combined prostate cancer tissues. Among the quantified proteins, DEPs were 865 (21.2%), those with a quantitative ratio greater than 2 were considered as upregulated, whereas those with a quantitative ratio of less than 0.5 as downregulated. Based on quantitative protein results, we performed systematic bioinformatics analysis including GO, Interpro, KEGG pathway, functional enrichment-based cluster analysis on DEPs. Finally, we found that 15 proteins including FOXA1 and HMGN1-3 between T3G3, T3GX, and CRPC were increased despite ADT treatment. Among all target, we verified increased level of FOXA1 and HMGN1-3 in CRPC by immunoblotting and indirect ELISA. In summary, we provides intracellular mechanical changes on PCa tissues according to treatment before and after ADT by mean of regulating ADT treatment. In addition, this results were identified through bioinformatics analysis, and those were suggested as potential CRPC-related factors.