Project description:We used microarrays to study the global gene expression and identified differentially expressed genes in PTEN knockout SF763 cells, aiming to identify genes and pathways that are regulated by PTEN.
Project description:MicroRNA profiling in Pten knockout mouse thymus cells. microRNAs (miRs) are short noncoding RNAs of 20â22 nucleotides that function to regulate gene expression at the posttranscriptional level. They play fundamental roles in the regulation of cellular proliferation, differentiation, and apoptosis. miRs are dysregulated in many types of cancer, including T-ALL (T cell lymphoblastic leukemia). miRs can function as oncogenes, favoring the initiation and progression of cancers, or as tumor suppressors, preventing tumorigenesis. The biological functions of miRs in T-ALL are largely unknown. In human T-ALL patients, recurrent mutations in the Phosphatase and tensin homolog (PTEN) gene are common, consistent with Pten-knockout mice developing T-ALL. To better understand T-ALL pathogenesis and identify new therapeutic targets in T-ALL, we developed a Pten-knockout T-ALL mouse model and the mice developed T-ALL within 3 months as expected. We profiled the miRs in the Pten-deficient mouse T-ALL. A576, A577, A578 and A579 are PTEN-knockout mouse T-ALL samples. A580 andA 581 are wild-type mouse thymocytes.
Project description:PTEN, a well-known tumor suppressor, negatively regulates the PI3K-AKT signaling pathway. Its loss is prevalent across various cancer types and leads to significant changes in cellular signaling networks. In this study, we investigate the effects of PTEN loss on both canonical PI3K-AKT and noncanonical tyrosine kinase pathways in MCF10A PTEN knockout (KO) cells. Through quantitative proteomics and phosphoproteomics, we identified substantial changes in protein and phosphorylation profiles, including key signaling regulators such as EphA2, Src, and MEK-ERK1/2. Our findings reveal that PTEN loss not only activates PI3K-AKT signaling but also elevates tyrosine kinase signaling, with Src kinase playing a crucial role in upregulating EphA2, an RTK implicated in tumor progression. Interestingly, inhibition of AKT alone did not consistently reduce EphA2 levels, highlighting an AKT-independent mechanism of EphA2 regulation via Src in PTEN-deficient cells. We demonstrated that combined targeting of AKT and Src pathways using Capivasertib (AKT inhibitor) and Dasatinib (Src inhibitor) significantly suppressed proliferation and induced apoptosis in PTEN-deficient breast and endometrial cancer cell lines, with notable synergy observed in patient-derived xenograft (PDX) models. These results suggest that dual inhibition of AKT and Src could provide a promising therapeutic approach for PTEN-deficient cancers, addressing resistance limitations associated with AKT inhibition alone and improving therapeutic efficacy. This study underscores the complex regulatory mechanisms involving PTEN and highlights new possibilities for targeted combination therapies in cancers with PTEN loss.
Project description:The goal of this study was to perform transcriptomics on wildtype, PTEN single knockout (SKO) and PTEN;Rb1 double knockout (DKO) mouse prostate organoids. We isolated basal cells from PTEN floxed and PTEN;Rb1 floxed mouse prostates and infected with either RFP control or Cre recombinase to establish wildtype, SKO, and DKO mouse prostate organoids.
Project description:extracellular PTEN treatment did not affect the growth of PTEN knockout B16-F10 cells cultured in vitro. , To investigate whether extracellular PTEN act on the tumor microenvironment to exert a tumor-suppressive role in vivo,molecular changes caused by PTEN treatment inside the B16-F10-PTEN tumors were monitored by RNA sequencing.
Project description:Interventions: experimental group :PD-1 Knockout Engineered T Cells
Primary outcome(s): Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
Study Design: historical control
Project description:Gene expression of hepatocyt-specific knockout of Pten and of Pten and Tgfbr2 in mice as a model for human cholangiocarcinoma was determined Affymetrix Mouse 1.0ST chips were used to measure gene expression Gene expression of the following mouse livers were characterized A. WT (n=3). B. Pten-/- (n=4). C. Pten-/- Tgfbr2-/- (n=4).
Project description:PTEN treatment can affect the tumor growth of PTEN knockout B16-F10 cells in C57BL/6J mice,We hope to analyze the changes that occur in various cells in tumors through single-cell RNA sequencing.
Project description:Gene expression of hepatocyt-specific knockout of Pten and of Pten and Tgfbr2 in mice as a model for human cholangiocarcinoma was determined Affymetrix Mouse 1.0ST chips were used to measure gene expression