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Astrocytoma Cell Lines (astrocytoma + cell_line)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Expression of multiple P2Y receptors by MDCK-D1 cells: P2Y1 receptor cloning and signaling

DRUG DEVELOPMENT RESEARCH, Issue 1 2003
Richard J. Hughes
The Madin Darby canine kidney (MDCK) cell line, a well-differentiated renal epithelial cell line, is a useful model to examine P2Y receptor signaling and response. Our studies with MDCK-D1, a clonal isolate, demonstrate that these cells release ATP in response to mechanical stimulation and activation of certain G-protein-coupled receptors. Reverse transcriptase-polymerase chain reaction (RT-PCR) studies document that MDCK cells express multiple P2Y receptors, including P2Y1, P2Y2, P2Y6, and P2Y11 receptors. We isolated cDNAs for several of the P2Y receptor genes and expressed these in cells, such as the 1321N1 astrocytoma cell line, that lack native P2Y receptor expression. We report here the molecular cloning of the MDCK P2Y1 receptor, heterologous expression in 1321N1 cells, and the ability of the heterologously expressed receptors to increase intracellular calcium and phosphoinositide hydrolysis. ADP, methylthioATP, and ADP,S are agonists with the greatest potency, while ATP and ATP,S show lower potency and efficacy, and benzoylbenzoylATP, UTP, and UDP lack efficacy at the cloned P2Y1 receptor. Several antagonists, including MRS2179, A3P5PS, suramin, and PPADS blocked response at the cloned P2Y1 receptors. With their ability to respond to ADP and ATP, P2Y1 receptors, along with other P2Y receptors expressed in MDCK cells, contribute to the response of these cells to ATP (or its breakdown product, ADP) released from the cells and to exogenously added nucleotides. Drug Dev. Res. 59:1,7, 2003. © 2003 Wiley-Liss, Inc. [source]

Prognostic significance of integrin-linked kinase1 overexpression in astrocytoma

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010
Jun Li
Abstract Integrin-linked kinase 1 (ILK1), a member of the serine/threonine kinases, has been demonstrated to be associated with numerous biological and pathological processes. However, the clinical and functional significance of ILK1 expression has not been characterized previously in human astrocytoma. In this study, we found that ILK1 was overexpressed, at both mRNA and protein levels, in astrocytoma cell lines as compared with normal human astrocytes. The ILK1 mRNA and protein were significantly increased up to 5.6-fold and 10.1-fold, respectively, in primary astrocytoma in comparison with the paired adjacent noncancerous brain tissues obtained from the same patient. Furthermore, immunohistochemical analysis revealed that ILK1 protein was positive in 208 of 228 (91.2%) paraffin-embedded archival astrocytoma specimens. Statistical analysis suggested that the upregulation of ILK1 was significantly correlated with the histological grading of astrocytoma (p = 0.000), and that patients with high ILK1 level exhibited shorter survival time (p < 0.001). Multivariate analysis revealed that ILK1 upregulation might be an independent prognostic indicator for the survival of patients with astrocytoma. Taken together, our results suggest that ILK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease. [source]

Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas

INTERNATIONAL JOURNAL OF CANCER, Issue 4 2008
Suely K.N. Marie
Abstract We have performed cDNA microarray analyses to identify gene expression differences between highly invasive glioblastoma multiforme (GBM) and typically benign pilocytic astrocytomas (PA). Despite the significant clinical and pathological differences between the 2 tumor types, only 63 genes were found to exhibit 2-fold or greater overexpression in GBM as compared to PA. Forty percent of these genes are related to the regulation of the cell cycle and mitosis. QT-PCR validation of 6 overexpressed genes: MELK, AUKB, ASPM, PRC1, IL13RA2 and KIAA0101 confirmed at least a 5-fold increase in the average expression levels in GBM. Maternal embryonic leucine zipper kinase (MELK) exhibited the most statistically significant difference. A more detailed investigation of MELK expression was undertaken to study its oncogenic relevance. In the examination of more than 100 tumors of the central nervous system, we found progressively higher expression of MELK with astrocytoma grade and a noteworthy uniformity of high level expression in GBM. Similar level of overexpression was also observed in medulloblastoma. We found neither gene promoter hypomethylation nor amplification to be a factor in MELK expression, but were able to demonstrate that MELK knockdown in malignant astrocytoma cell lines caused a reduction in proliferation and anchorage-independent growth in in vitro assays. Our results indicate that GBM and PA differ by the expression of surprisingly few genes. Among them, MELK correlated with malignancy grade in astrocytomas and represents a therapeutic target for the management of the most frequent brain tumors in adult and children. © 2007 Wiley-Liss, Inc. [source]

Biomolecular characterization of human glioblastoma cells in primary cultures: Differentiating and antiangiogenic effects of natural and synthetic PPAR, agonists

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2008
E. Benedetti
Gliomas are the most commonly diagnosed malignant brain primary tumors. Prognosis of patients with high-grade gliomas is poor and scarcely affected by radiotherapy and chemotherapy. Several studies have reported antiproliferative and/or differentiating activities of some lipophylic molecules on glioblastoma cells. Some of these activities in cell signaling are mediated by a class of transcriptional factors referred to as peroxisome proliferator-activated receptors (PPARs). PPAR, has been identified in transformed neural cells of human origin and it has been demonstrated that PPAR, agonists decrease cell proliferation, stimulate apoptosis and induce morphological changes and expression of markers typical of a more differentiated phenotype in glioblastoma and astrocytoma cell lines. These findings arise from studies mainly performed on long-term cultured transformed cell lines. Such experimental models do not exactly reproduce the in vivo environment since long-term culture often results in the accumulation of further molecular alterations in the cells. To be as close as possible to the in vivo condition, in the present work we investigated the effects of PPAR, natural and synthetic ligands on the biomolecular features of primary cultures of human glioblastoma cells derived from surgical specimens. We provide evidence that PPAR, agonists may interfere with glioblastoma growth and malignancy and might be taken in account as novel antitumoral drugs. J. Cell. Physiol. 217: 93,102, 2008. © 2008 Wiley-Liss, Inc. [source]