Limitless reproductive potential is one of the hallmarks of cancer cells1. This ability is accomplished by maintaining telomeres, which erosion otherwise causes cellular senescence or death. Human cancer cells often maintain shorter telomeres than do cells in surrounding normal tissues2-5. While most cancer cells activate telomerase, which can elongate telomeres6, it remains elusive why cancer cells keep telomeres short. Here we show that forced elongation of telomeres in cancer cells promotes their differentiation in a tumor microenvironment in vivo. We elongated telomeres of human prostate cancer PC-3 cells, which possess short telomeres7, by enhancing their telomerase activity. The resulting cells with long telomeres retain an ability to form tumors in a mouse xenograft model. Strikingly, these tumors exhibit many duct-like structures and reduced N-cadherin expression, reminiscent of well-differentiated adenocarcinoma. These phenotypic changes are caused by telomere elongation per se but not enhanced telomerase activity. Gene expression profiling revealed that telomere elongation correlates with inhibition of cell-cycle processes. Together, our results suggest a functional contribution of short telomeres to tumor malignancy by regulating cancer cell differentiation.
Telomere length influences cancer cell differentiation in vivo.
Cell line
View SamplesLimitless reproductive potential is one of the hallmarks of cancer cells1. This ability is accomplished by maintaining telomeres, which erosion otherwise causes cellular senescence or death. Human cancer cells often maintain shorter telomeres than do cells in surrounding normal tissues2-5. While most cancer cells activate telomerase, which can elongate telomeres6, it remains elusive why cancer cells keep telomeres short. Here we show that forced elongation of telomeres in cancer cells promotes their differentiation in a tumor microenvironment in vivo. We elongated telomeres of human prostate cancer PC-3 cells, which possess short telomeres7, by enhancing their telomerase activity. The resulting cells with long telomeres retain an ability to form tumors in a mouse xenograft model. Strikingly, these tumors exhibit many duct-like structures and reduced N-cadherin expression, reminiscent of well-differentiated adenocarcinoma. These phenotypic changes are caused by telomere elongation per se but not enhanced telomerase activity. Gene expression profiling revealed that telomere elongation correlates with inhibition of cell-cycle processes. Together, our results suggest a functional contribution of short telomeres to tumor malignancy by regulating cancer cell differentiation.
Telomere length influences cancer cell differentiation in vivo.
Cell line
View SamplesWe show that highly metastatic mouse melanoma B16/BL6 cells express less Gal-3 than B16 cells with a lower metastatic potential. We found that overexpression of Gal-3 in melanoma cells in fact suppresses metastasis. In contrast, knocking out Gal-3 expression in cancer cells promoted cell aggregation mediated through interactions with platelets and fibrinogen in vitro, and increased the number of metastatic foci in vivo. Overall design: We search for metastatic related gene in melanoma cells. Cells were removed in culture dish and total RNA was extracted from cells using Rneasy-plus mini kits. We compared the gene expression of B16 cells and B16/BL6 cells.
Galectin-3 Inhibits Cancer Metastasis by Negatively Regulating Integrin β3 Expression.
Specimen part, Cell line, Subject
View SamplesGoal of experiment: Identify genes down-regulated between pre- and post-natal stages in mouse dental papillae.
Down-regulated genes in mouse dental papillae and pulp.
No sample metadata fields
View SamplesMost human B cell lymphomas (B-NHL) are derived from germinal centers (GCs), the structure where B-cells undergo class switch recombination (CSR) and somatic hypermutation (SHM) and are selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant somatic hypermutation, which appear to arise from mistakes occurring during CSR and SHM. To ascertain the role of CSR and SHM in lymphomagenesis, we crossed three oncogene-driven (MYC, BCL6, MYC/BCL6) mouse models of B cell lymphoma with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both processes.
AID is required for germinal center-derived lymphomagenesis.
Specimen part
View SamplesTankyrase enhances beta-catenin signaling via PARsylation and subsequent degradation of Axin, a negative regulator of beta-catenin. Tankyrase inhibitors stabilize Axin and suppress beta-catenin signaling. We developed a novel tankyrase inhibitor, RK-287107.
RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model.
Specimen part, Treatment
View SamplesThe balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) maintains hematopoietic homeostasis, failure of which can lead to hematopoietic disorder. HSPC fate is controlled by signals from the bone marrow niche resulting in alteration of the stem cell transcription network. Regnase-1, a member of the CCCH zinc finger protein family possessing RNAse activity, mediates post-transcriptional regulatory activity through degradation of target mRNAs. The precise function of Regnase-1 has been explored in inflammation-related cytokine expression but its function in hematopoiesis has not been elucidated. To clarify the role of Regnase-1 for hematopoiesis, we performed gene expression analysis on sorted HSC from control and Regnase1 null mice. Overall design: Bone marrow cells were obtained from femur of individual eight-week old Vav1-iCre; Reg1flox/flox mice (Reg1?/?, case) and control Reg1flox/flox mice (Reg1flox/flox ,control). RNAseq analyses were performed on HSCs (Lin- ScaI+ cKit+ CD34- Flt3- cells) purified by flow cytometry sorting.
Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis.
Specimen part, Cell line, Subject
View SamplesTH-MYCN transgenic (Tg) mice are the model for neuroblastoma. One of the sympathetic ganglia is the origin of neuroblastoma in those mice. The tumor incidences of homozygotes and hemizygotes are 100% and 70-80%, respectively.
Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.
Specimen part
View SamplesTo examine irreversible changes in the developing brain following seizures, juvenile inbred mice were intraperitoneally injected with kainate and nicotine.
Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures.
No sample metadata fields
View SamplesArabidopsis Nudix hydrolases, AtNUDX6 and 7, exhibit pyrophosphohydrolase activities toward NADH and contribute to the modulation of various defense responses, such as the poly(ADP-ribosyl)ation (PAR) reaction and salicylic acid (SA)-induced Nonexpresser of Pathogenesis-Related genes 1 (NPR1)-dependent defense pathway, against biotic and abiotic stresses.
Modulation of NADH Levels by Arabidopsis Nudix Hydrolases, AtNUDX6 and 7, and the Respective Proteins Themselves Play Distinct Roles in the Regulation of Various Cellular Responses Involved in Biotic/Abiotic Stresses.
Specimen part
View Samples