Search results for "PROLIFERATION"
showing 10 items of 1193 documents
HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion.
2008
The cancer stem cell hypothesis proposes that cancers arise in stem/progenitor cells through disregulation of self-renewal pathways generating tumors, which are driven by a component of 'tumor-initiating cells' retaining stem cell properties. The HER2 gene is amplified in 20-30% of human breast cancers and has been implicated in mammary tumorigenesis as well as in mediating aggressive tumor growth and metastasis. We demonstrate that HER2 overexpression drives mammary carcinogenesis, tumor growth and invasion through its effects on normal and malignant mammary stem cells. HER2 overexpression in normal mammary epithelial cells (NMEC) increases the proportion of stem/progenitor cells as demons…
Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.
2014
Peripheral T-cell lymphomas not otherwise specified (PTCL/NOS) are very aggressive tumors characterized by consistent aberrant expression of platelet-derived growth factor receptor alpha (PDGFRA). In this study, we aimed to identify the determinants of PDGFRA activity in PTCL/NOS and to elucidate the biological consequences of its activation. We observed overexpression of the PDGFRA gene by gene expression profiling in most of the tested PTCLs and confirmed the expression of PDGFRA and phospho-PDGFRA using immunohistochemistry. The integrity of the PDFGRA locus was demonstrated using several different approaches, including massive parallel sequencing and Sanger sequencing. PDGF-AA was found…
Molecular principles of cancer invasion and metastasis (Review)
2009
The main threat and the reason for most cancer deaths are not the primary neoplasias, but secondary tumors, the metastases. Drastic phenotypic and biochemical changes occur during the metamorphosis of a normal tissue cell into an invasive cancer cell. These alterations concern various areas such as growth factor signaling, cell-cell adhesion, gene expression, motility or cell shape. Cancer cells of epithelial origin can even shed their typical qualities and characteristics and adopt a mesenchymal-like phenotype. This is often referred to as an epithelial-mesenchymal transition. Various oncogenes, tumor suppressor genes and metastasis suppressor genes are known to affect the invasiveness and…
MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts
2013
The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect and a hyp…
Bovine seminal ribonuclease is cytotoxic for both malignant and normal telomerase-positive cells
2005
Bovine seminal-ribonuclease (BS-RNase) is a member of the 'ribonucleases with special biological actions' family since it possesses specific anti-tumour, anti-spermatogenic and embryotoxic activities and exerts an immunosuppressive effect on T lymphocytes. In previous studies it was demonstrated that BS-RNase induced apoptosis in proliferating, malignant and normal cells and that telomerase activity loss also caused apoptotic death in neoplastic cells. Since an obvious relationship between cell proliferation and telomerase activity exists, the aim of this work was to study if the pro-apoptotic cytotoxic action exerted by BS-RNase on proliferating malignant cells (HT29) and proliferating nor…
Bmi1 and Cell of Origin Determinants of Brain Tumor Phenotype
2007
Glioblastomas frequently express oncogenic EGFR and loss of the Ink4a/Arf locus. Bmi1, a positive regulator of stem cell self renewal, may be critical to drive brain tumor growth. In this issue of Cancer Cell, Bruggeman and colleagues suggest that brain tumors with these molecular alterations can be initiated in both neural precursor and differentiated cell compartments in the absence of Bmi1; however, tumorigenicity is reduced, and tumors contain fewer precursor cells. Surprisingly, tumors appear less malignant when initiated in precursor cells. Bmi1-deficient tumors also had fewer neuronal lineage cells, suggesting a role for Bmi1 in determination of cell lineage and tumor phenotype.
hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
2022
Abstract Background The tyrosine kinase receptor encoded by the MET oncogene is a major player in cancer. When MET is responsible for the onset and progression of the transformed phenotype (MET-addicted cancers), an efficient block of its oncogenic activation results in potent tumor growth inhibition. Methods Here we describe a molecular engineered MET antibody (hOA-DN30) and validate its pharmacological activity in MET-addicted cancer models in vitro and in vivo. Pharmacokinetics and safety profile in non-human primates have also been assessed. Results hOA-DN30 efficiently impaired MET activation and the intracellular signalling cascade by dose and time dependent removal of the receptor fr…
Analysis of Antiproliferative and Chemosensitizing Effects of Sunitinib on Human Esophagogastric Cancer Cells: Synergistic Interaction With Vandetani…
2009
The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1-3 (VEGFR1-3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti-proliferative and chemosensitizing properties of the multitargeted small-molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small-molecule inhibitors was examined by reverse transcriptase-polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, …
Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T315I Bcr-Abl mutant by a redox-mediated me…
2010
Mutation of the Bcr–Abl oncoprotein is one of most frequent mechanisms by which chronic myelogenous leukemia (CML) cells become resistant to imatinib. Here, we show that treat- ment of cell lines harbouring wild type or mutant BCR–ABL with carboxyamidotriazole (CAI), a calcium influx and signal transduction inhibitor, inhibits cell growth, the expres- sion of Bcr–Abl and its downstream signalling, and induces apoptosis. Moreover, we show that CAI acts by increasing intracellular ROS. Clinically significant, CAI has also inhibitory effects on T315I Bcr–Abl mutant, a mutation that causes CML cells to become insensitive to imatinib and second generation abl kinase inhibitors.
aPKCζ cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia
2007
Atypical protein kinase C (aPKC) and Lethal giant larvae (Lgl) regulate apical-basal polarity in Drosophila and mammalian epithelia. At the apical domain, aPKC phosphorylates and displaces Lgl that, in turn, maintains aPKC inactive at the basolateral region. The mutual exclusion of these two proteins seems to be crucial for the correct epithelial structure and function. Here we show that a cortical aPKC loading induces Lgl cytoplasmic release and massive overgrowth in Drosophila imaginal epithelia, whereas a cytoplasmic expression does not alter proliferation and epithelial overall structure. As two aPKC isoforms (iota and zeta) exist in humans and we previously showed that Drosophila Lgl i…