A5028294868- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Bone and Dental Protein Studies
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- American Environmental and Regional History
- Cancer Genomics and Diagnostics
- Signaling Pathways in Disease
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Wnt/β-catenin signaling in development and cancer
- Virus-based gene therapy research
- Historical Architecture and Urbanism
- PARP inhibition in cancer therapy
- Blood Coagulation and Thrombosis Mechanisms
- DNA Repair Mechanisms
- Historical Economic and Social Studies
- Advanced Proteomics Techniques and Applications
- Cancer-related Molecular Pathways
- TGF-β signaling in diseases
- History and Developments in Astronomy
- Cancer-related gene regulation
- Growth Hormone and Insulin-like Growth Factors
University Health Network
2014-2024
Princess Margaret Cancer Centre
2015-2024
University of Toronto
2001-2023
Ontario Institute for Cancer Research
1994-2020
Amgen (Canada)
1994-2001
Muscular Dystrophy Canada
2001
Cancer Institute (WIA)
1998
Western University
1986-1993
Hospital de Sant Pau
1988
University of Ottawa
1983
The absence of CTLA-4 results in uncontrolled T cell proliferation. receptor-specific kinases FYN, LCK, and ZAP-70 as well the RAS pathway were found to be activated cells Ctla-4-/- mutant mice. In addition, specifically associated with tyrosine phosphatase SYP, an interaction mediated by SRC homology 2 (SH2) domains SYP phosphotyrosine sequence Tyr-Val-Lys-Met within cytoplasmic tail. CTLA-4-associated had activity toward regulator p52SHC. Thus, activation through receptor are regulated SYP.
Mouse 3T3 cell lines capable of constitutively synthesizing an RNA complementary to the messenger encoding TIMP, tissue inhibitor metalloproteinases, were constructed by transfection with appropriate plasmid constructs. Many down-modulated for TIMP levels and secreted less into culture medium. In comparison noninvasive, nontumorigenic controls, these cells not only invasive in a human amnion invasion assay, but also tumorigenic metastatic athymic mice. These results indicate that suppresses...
Tissue inhibitors of metalloproteinases regulate ECM degradation by matrix (MMPs). We have developed a mouse line deficient for tissue inhibitor metalloproteinases-3 (TIMP-3), the only TIMP known to reside within ECM. Homozygous Timp-3–null animals develop spontaneous air space enlargement in lung that is evident at 2 weeks after birth and progresses with age animal. As early as 13 months become moribund. Lung function, measured carbon monoxide uptake, impaired aged null animals. Lungs from...
Tissue inhibitors of metalloproteinases regulate ECM degradation by matrix (MMPs). We have developed a mouse line deficient for tissue inhibitor metalloproteinases-3 (TIMP-3), the only TIMP known to reside within ECM. Homozygous Timp-3–null animals develop spontaneous air space enlargement in lung that is evident at 2 weeks after birth and progresses with age animal. As early as 13 months become moribund. Lung function, measured carbon monoxide uptake, impaired aged null animals. Lungs from...
We present the DNA sequence of an essentially full-length cDNA clone 16C8, a growth factor-inducible gene isolated from mouse embryo fibroblast library. The 0.9-kb mRNA encodes Mr 22,500 protein that has substantial homology to human with reported abilities potentiate erythroid differentiation and inhibit collagenases other tissue metalloproteinases. N-terminus predicted hydrophobic nature characteristic secreted proteins, two potential sites for N-linked glycosylation are present....
The proapoptotic proteinase inhibitor TIMP-3 is the only molecule of this family thought to influence cell death. We examined epithelial apoptosis in TIMP-3–deficient mice during mammary gland involution. Lactation was not affected by absence TIMP-3, but glandular function, as measured gland-to-body weight ratio and production β-casein, suppressed earlier post-lactational involution than controls. Histological examination revealed accelerated lumen collapse, alveolar-epithelial loss, adipose...
The proapoptotic proteinase inhibitor TIMP-3 is the only molecule of this family thought to influence cell death. We examined epithelial apoptosis in TIMP-3–deficient mice during mammary gland involution. Lactation was not affected by absence TIMP-3, but glandular function, as measured gland-to-body weight ratio and production β-casein, suppressed earlier post-lactational involution than controls. Histological examination revealed accelerated lumen collapse, alveolar-epithelial loss, adipose...
We have previously shown that down-modulation (i.e., by antisense expression vector) of tissue inhibitor metalloproteinase-1 (TIMP-1) in a noninvasive, nontumorigenic cell line led to an acquisition invasive, tumorigenic, and metastatic ability these cells.Our purpose was examine whether increased levels murine TIMP-1 can directly suppress the invasive malignant cells.Murine B16-F10 melanoma cells were transfected with vector overproduce TIMP-1. Among transfectants, we isolated five clonal...
Denosumab, an antibody targeting RANKL, is effective against osteosarcoma in mouse models.
Systemic and local signals must be integrated by mammary stem progenitor cells to regulate their cyclic growth turnover in the adult gland. Here, we show RANK-positive luminal progenitors exhibiting WNT pathway activation are selectively expanded human breast during progesterone-high menstrual phase. To investigate underlying mechanisms, examined mouse models found that loss of RANK prevents proliferation hormone receptor-negative basal cells, an accompanying activation, and, hence, a...
Leveraging the conserved cancer genomes across mammals has potential to transform driver gene discovery in orphan cancers. Here, we combine cross-species genomics with validation human-dog-mouse systems uncover a new bone tumor suppressor gene. Comparative of spontaneous human and dog osteosarcomas (OS) expose Disks Large Homolog 2 (DLG2) as candidate. DLG2 copy number loss occurs 42% 56% canine OS. Functional through pertinent OS DLG2-deficient cell lines identifies regulatory role...
BACKGROUND Altered expression and activity of proteases is implicated in inflammation cancer progression. An important negative regulator protease TIMP3 (tissue inhibitor metalloproteinase 3). lacking many cancers including advanced prostate cancer, this may facilitate invasion metastasis by allowing unrestrained activity. METHODS To investigate the role progression, we crossed TIMP3-deficient mice (Timp3−/−) to with prostate-specific deletion tumor suppressor Pten (Pten−/−), a...
Abstract The mammary gland experiences substantial remodeling and regeneration during development reproductive life, facilitated by stem cells progenitors that act in concert with physiological stimuli. While studies have focused on deciphering regenerative within the parenchymal epithelium, cell lineages stroma may directly contribute to epithelial biology is unknown. Here we identify, mouse, transition of a PDGFRα + mesenchymal population into progenitors. In addition being adipocyte...
Abstract Tissue inhibitors of metalloproteinases (TIMPs) appear to play an important regulatory role in tissue remodelling and invasion by malignant cells. Since pregnancy involves morphological changes existing maternal tissues, as well a strictly controlled fetal trophoblasts, we have examined the temporal expression TIMP‐1, TIMP‐2, specific mouse uterus, decidua, placenta, amnion, ovaries throughout gestation examining mRNA levels on northern slot blots. Maximal TIMP‐1 were observed from...
The mammary epithelium depends on specific lineages and their stem progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these underpin breast cancer risk, yet our understanding normal cell composition is incomplete. Here, we build a multimodal resource for gland through comprehensive profiling primary epigenomes, transcriptomes, proteomes. We define systems-level relationships between chromatin–DNA–RNA–protein states, identify...
Progesterone drives mammary stem and progenitor cell dynamics through paracrine mechanisms that are currently not well understood. Here, we demonstrate CXCR4, the receptor for stromal-derived factor 1 (SDF-1; CXC12), is a crucial instructor of hormone-induced function. elicits specific changes in transcriptome basal luminal epithelial populations, where CXCL12 CXCR4 represent putative ligand-receptor pair. In situ, localizes to progesterone-receptor-positive cells, whereas induced both...
CTLA-4 has been proposed to negatively regulate immune responses, and mice deficient for expression succumb a lymphoproliferative disorder within few weeks after birth. This study assessed the responsiveness of CTLA-4-deficient T cells expressing class I-restricted TCR specific lymphocytic choriomeningitis virus (LCMV). The kinetics cell proliferation were studied in vitro stimulation with full partial agonists. No gross abnormalities could be detected. Using adoptive transfer experiments,...