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Variety Of Cellular Functions (variety + of_cellular_function)
Selected AbstractsExpression and mutational analysis of MET in human solid cancersGENES, CHROMOSOMES AND CANCER, Issue 12 2008Patrick C. Ma MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring system were used. DNA sequencing for MET mutations in both nonkinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumors, primarily intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression. MET would be an important therapeutic antitumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker. © 2008 Wiley-Liss, Inc. [source] Toxicogenomics: a pivotal piece in the puzzle of toxicological researchJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007Elisavet T. Gatzidou Abstract Toxicogenomics, resulting from the merge of conventional toxicology with functional genomics, being the scientific field studying the complex interactions between the cellular genome, toxic agents in the environment, organ dysfunction and disease state. When an organism is exposed to a toxic agent the cells respond by altering the pattern of gene expression. Genes are transcribed into mRNA, which in turn is translated into proteins that serve in a variety of cellular functions. Toxicogenomics through microarray technology, offers large-scale detection and quantification of mRNA transcripts, related to alterations in mRNA stability or gene regulation. This may prove advantageous in toxicological research. In the present review, the applications of toxicogenomics, especially to mechanistic and predictive toxicology are reported. The limitations arising from the use of this technology are also discussed. Additionally, a brief report of other approaches, using other -omic technologies (proteomics and metabonomics) that overcome limitations and give global information related to toxicity, is included. Copyright © 2007 John Wiley & Sons, Ltd. [source] WDR26: A novel G,-like protein, suppresses MAPK signaling pathway,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2004Ying Zhu Abstract WD40 repeat proteins play important roles in a variety of cellular functions, including cell growth, proliferation, apoptosis, and intracellular signal transduction. Mitogen-activated protein kinases (MAPKs) are evolutionary conserved enzymes in cell signal transduction connecting cell-surface receptors to critical regulatory targets within cells and control cell survival, adaptation, and proliferation. Previous studies revealed that G-protein coupled receptors (GPCRs) play important roles in the signal transduction from extracellular stimuli to MAPKs and the WD40-containing G, proteins as well as G,-like proteins are involved in the stimulation and regulation of the MAPK signaling pathways. Here we report the identification and characterization of a novel human WD40 repeat protein, WD40 repeat protein 26 (WDR26). The cDNA of WDR26 is 3,729 bp, encoding a G,-like protein of 514 amino acids in the cytoplasm. The protein is highly conserved in evolution across different species from yeast, Drosophila, mouse, to human. Northern blot analysis indicates that WDR26 is expressed in most of the examined human tissues, especially at a high level in skeletal muscle. Overexpression of WDR26 in the cell inhibits the transcriptional activities of ETS proteins, ELK-1 and c-fos serum response element (SRE), mediated by MEKK1. These results suggest that WDR26 may act as a negative regulator in MAPK signaling pathway and play an important role in cell signal transduction. © 2004 Wiley-Liss, Inc. [source] Emerging functions of p21-activated kinases in human cancer cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2002Rakesh Kumar The p21 activated kinases (Paks), an evolutionarily conserved family of serine/threonine kinases, are important for a variety of cellular functions including cell morphogenesis, motility, survival, mitosis, and angiogenesis. Paks are widely expressed in numerous tissues and are activated by growth factors and extracellular signals through GTPase-dependent and -independent mechanisms. Overexpression of Paks in epithelial cancer cells has been shown to increase migration potential, increase anchorage independent growth, and cause abnormalities in mitosis. Dysregulation of Paks has been reported in several human tumors and neurodegenerative diseases. A growing list of novel Pak interacting proteins has opened up exciting avenues of investigation by which to understand the functions of Paks in tumorigenesis. In this review, we will summarize the current knowledge of the Paks family with respect to emerging cellular functions and possible contributions to cancer. © 2002 Wiley-Liss, Inc. [source] Rac1 inhibition negatively regulates transcriptional activity of the amyloid precursor protein geneJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2009Pi-Lin Wang Abstract Rac1, a member of the Rho family GTPases, participates in a variety of cellular functions including lamellipodia formation, actin cytoskeleton organization, cell growth, apoptosis, and neuronal development. Recent studies have implicated Rac1 in cytoskeletal abnormalities, production of reactive oxygen species, and generation of the amyloid ,-peptide (A,) observed in Alzheimer's disease. In this study, we examined the relationship between Rac1 and amyloid precursor protein (APP), because the abnormal proteolytic processing of APP is a pathologic feature of Alzheimer's disease. In primary hippocampal neurons, the Rac1-specific inhibitor NSC23766 decreased both Rac1 activity and APP protein levels in a concentration-dependent manner. To elucidate how NSC23766 decreases APP protein levels, we examined the effects of NSC23766 on APP processing, degradation, and biosynthesis. NSC23766 did not increase the levels of the proteolytic products of APP, sAPP,, A,40, and A,42. The proteasome inhibitor lactacystin did not reverse the NSC23766-induced decrease in APP protein levels. NSC23766 did, however, decrease the levels of both APP mRNA and APP protein. Decreased levels of APP mRNA and protein were also observed when HEK293 cells were transfected with an expression vector containing a dominant-negative Rac1 mutant or with siRNA targeting Rac1. By overexpressing progressively deleted fragments of the APP promoter in HEK293 cells, we identified a Rac1 response site at positions ,233 to ,41 bp in the APP promoter. Taken together, our results suggest that Rac1 regulates transcription of the APP gene in primary hippocampal neurons. © 2009 Wiley-Liss, Inc. [source] The expression pattern of PKC, in satellite cells of normal and regenerating muscle in the ratNEUROPATHOLOGY, Issue 3 2009Seiji Tokugawa Protein kinase C (PKC) is a key enzyme in regulating a variety of cellular functions. PKC, is the most abundant PKC isoform expressed in skeletal muscle. However, the functional role of PKC, linked to muscle regeneration has not yet been identified. Using reverse transcription (RT)-PCR and immunofluorescence analysis, we investigated the expression patterns of PKC, in normal and regenerating tibialis anterior (TA) muscles in the rat. The amount of PKC, mRNA in the muscle increased from the 4th to 6th post-surgical day. Immunofluorescence revealed PKC, protein in quiescent satellite cells identified by c-Met. PKC, immunoreactivity was not observed in many proliferating satellite cells by labeling with BrdU in the regenerating muscle. At 4, 6 and 10 days postsurgery, PKC, immunoreactivity was observed in half the differentiating satellite cells labeling with myogenin. After 4 and 6 days, the localization of PKC, coincided with those of Pax7 and TGF-,. Thus, PKC, may play an important role in inhibiting differentiation and maintaining the quiescent satellite cells in muscle regeneration. [source] Structural and biochemical characterization of a novel Mn2+ -dependent phosphodiesterase encoded by the yfcE genePROTEIN SCIENCE, Issue 7 2007Darcie J. Miller Abstract Escherichia coli YfcE belongs to a conserved protein family within the calcineurin-like phosphoesterase superfamily (Pfam00149) that is widely distributed in bacteria and archaea. Superfamily members are metallophosphatases that include monoesterases and diesterases involved in a variety of cellular functions. YfcE exhibited catalytic activity against bis- p -nitrophenyl phosphate, a general substrate for phosphodiesterases, and had an absolute requirement for Mn2+. However, no activity was observed with phosphodiesters and over 50 naturally occurring phosphomonoesters. The crystal structure of the YfcE phosphodiesterase has been determined to 2.25 Å resolution. YfcE has a ,-sandwich architecture similar to metallophosphatases of common ancestral origin. Unlike its more complex homologs that have added structural elements for regulation and substrate recognition, the relatively small 184-amino-acid protein has retained its ancestral simplicity. The tetrameric protein carries two zinc ions per active site from the E. coli extract that reflect the conserved di-Mn2+ active site geometry. A cocrystallized sulfate inhibitor mimics the binding of phosphate moeities in known ligand/phosphatase complexes. Thus, YfcE has a similar active site and biochemical mechanism as well-characterized superfamily members, while the YfcE phosphodiester-containing substrate is unique. [source] Analysis of vitamin D-regulated gene expression in LNCaP human prostate cancer cells using cDNA microarraysTHE PROSTATE, Issue 3 2004Aruna V. Krishnan Abstract BACKGROUND 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] exerts growth inhibitory, pro-differentiating, and pro-apoptotic effects on prostate cells. To better understand the molecular mechanisms underlying these actions, we employed cDNA microarrays to study 1,25(OH)2D3 -regulated gene expression in the LNCaP human prostate cancer cells. METHODS mRNA isolated from LNCaP cells treated with vehicle or 50 nM 1,25(OH)2D3 for various lengths of time were hybridized to microarrays carrying approximately 23,000 genes. Some of the putative target genes revealed by the microarray analysis were verified by real-time PCR assays. RESULTS 1,25(OH)2D3 most substantially increased the expression of the insulin-like growth factor binding protein-3 (IGFBP-3) gene. Our analysis also revealed several novel 1,25(OH)2D3 -responsive genes. Interestingly, some of the key genes regulated by 1,25(OH)2D3 are also androgen-responsive genes. 1,25(OH)2D3 also down-regulated genes that mediate androgen catabolism. CONCLUSIONS The putative 1,25(OH)2D3 target genes appear to be involved in a variety of cellular functions including growth regulation, differentiation, membrane transport, cell,cell and cell,matrix interactions, DNA repair, and inhibition of metastasis. The up-regulation of IGFBP-3 gene has been shown to be crucial in 1,25(OH)2D3 -mediated inhibition of LNCaP cell growth. 1,25(OH)2D3 regulation of androgen-responsive genes as well as genes involved in androgen catabolism suggests that there are interactions between 1,25(OH)2D3 and androgen signaling pathways in LNCaP cells. Further studies on the role of these genes and others in mediating the anti-cancer effects of 1,25(OH)2D3 may lead to better approaches to the prevention and treatment of prostate cancer. © 2004 Wiley-Liss, Inc. [source] Localization of Hyaluronic Acid in the Seminal Vesicles of the Miniature PigANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2007A. Sakairi Summary We studied the detailed localization of hyaluronic acid in the seminal vesicles of the miniature pig, using hyaluronic acid-binding protein as a specific histochemical probe at the ultrastructural level. According to the results, the basolateral surface of the plasma membrane of the glandular epithelial cells, was found to contain hyaluronan. However, abundantly present was hyaluronan in the subepithelial connective tissue, in particular, in the extracellular matrix surrounding the fibroblasts, smooth muscle cells, small blood vessels and capillaries. The substance was also observed in the surface coat of the plasma membrane of the fibroblasts, but not in that of the smooth muscle cells. The findings suggest that hyaluronan in the seminal vesicles of the miniature pig is synthesized onto the surface coat of the plasma membrane of the fibroblasts, is contributed to the extracellular matrix, and consequently concentrates in the subepithelial connective tissue. The substance may particularly be involved in a variety of cellular functions to maintain morphological organization as well as to regulate physiological homeostasis in the reproductive organ of this species, rather than participate in sperm functions. [source] Caveolin-1 is expressed on multipotent cells of hair follicles and might be involved in their resistance to chemotherapyBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2005S. Selleri Summary Background, Caveolin-1 is the principal protein that composes caveolae, which are vesicular invaginations present on the plasma membrane of different cell types. Caveolae are involved in a variety of cellular functions including regulation of proliferation rate and resistance to chemotherapeutic drugs. Chemotherapy frequently induces alopecia which is reversible most probably due to the low proliferative rate of hair follicle stem cells and due to the expression of proteins which confer resistance. Objectives, Using a specific animal model and immunohistochemistry, we analysed the expression of both caveolin-1 and the cell proliferation marker ,-catenin, at different stages of the hair follicle cycle, both before and after doxorubicin (DXR) -induced alopecia. Methods, Seven-week-old C57BL/6 mice were depilated in order to synchronize hair follicle cycle in the anagen phase. Chemotherapy with DXR 15 mg kg,1 was used to induce alopecia. Control and treated mice were then sacrificed at precise time points and caveolin-1 expression in hairs at different stages of the cycle were analysed by immunohistochemistry. By double immunofluorescence, colocalization of caveolin-1 and cytokeratin-15 was confirmed in the bulge region. The state of proliferation of cells composing hair follicle was assessed by ,-catenin immunohistochemistry. Results, Caveolin-1 was expressed by the cells of the bulge area, the multipotent compartment of the hair follicle, during all phases of growth (anagen), regression (catagen) and resting (telogen). During the anagen phases, nuclear ,-catenin labelling was not observed in bulge cells, but rather in the deeper portion of the follicle. Damaged hair follicles from DXR-treated mice presented bulge cells which still expressed caveolin-1, suggesting that this protein might play a role in their drug resistance. As expected, no ,-catenin nuclear staining was detectable in DXR-treated hair follicles, indicating the complete lack of proliferative processes. The differential localization of caveolin-1 and ,-catenin suggests that the mutually exclusive expression of these proteins is useful for correct hair regrowth, whether during the physiological cycle or after chemotherapy-induced alopecia. Conclusions, Expression of caveolin-1 within the multipotent cell compartment of the hair follicle can explain the resistance of bulge cells to many chemotherapeutics, suggested by the reversibility of chemotherapy-induced alopecia. [source] | ||||||||||||||||