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Induced Cell Proliferation (induced + cell_proliferation)
Selected AbstractsProstaglandin E2 promotes cell proliferation via protein kinase C/extracellular signal regulated kinase pathway-dependent induction of c-Myc expression in human esophageal squamous cell carcinoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 11 2009Le Yu Abstract Overexpression of cyclooxygenase-2 (COX-2) and elevation of its derivative prostaglandin E2 (PGE2) are implicated in human esophageal squamous cell carcinoma. The expression of c-Myc, an oncogenic transcription factor, is also upregulated in this malignant disease. This study sought to elucidate whether a functional connection exists between COX-2/PGE2 and c-Myc in esophageal squamous cell carcinoma. Results showed that PGE2 substantially increased the proliferation of cultured esophageal squamous cell carcinoma cells. In this regard, PGE2 substantially increased the mRNA and protein expression of c-Myc and its association with the binding partner Max. Knockdown of c-Myc by RNA interference also significantly attenuated PGE2 -induced cell proliferation. Further, mechanistic study revealed that PGE2 increased the protein stability and nuclear accumulation of c-Myc via phosphorylation on serine 62 in an extracellular signal regulated kinase (ERK)-dependent manner. To this end, ERK activation by PGE2 was completely abolished by protein kinase C (PKC) inhibitors. Moreover, the effect of PGE2 on c-Myc expression was mimicked by EP2 receptor agonist. In addition, knockdown of EP2 receptor by EP2 siRNA attenuated PGE2 -induced c-Myc expression. Collectively, our findings suggest that PGE2 upregulates c-Myc via the EP2/PKC/ERK pathway. This study sheds new light on the carcinogenic mechanism of PGE2 in esophageal squamous cell carcinoma. © 2009 UICC [source] Cimetidine inhibits epidermal growth factor-induced cell signalingJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2007Tatsuya Fujikawa Abstract Background:, Cimetidine, a histamine-2 (H2) receptor antagonist, has been demonstrated to have anticancer effects on colorectal cancer, melanoma and renal cell carcinoma. In the current study, we clarified that cimetidine inhibits both epidermal growth factor (EGF)-induced cell proliferation and migration in hepatocellular carcinoma (HCC) cell lines. Method:, HCC cell lines (Hep3B, HLF, SK-Hep-1, JHH-2, PLC/PRF/5 and HLE) were used and cell proliferation was assessed by [3H]-thymidine incorporation assay. Cell migration was measured by in vitro cell migration assay. Biological effects of cimetidine were assessed with human EGF receptor (EGFR)-expressing mouse fibroblast cells (NR6-WT). The autophosphorylation of EGFR and the activation of other downstream effectors were analyzed by immunoprecipitation and immunoblotting. The concentration of intracellular cyclic AMP (cAMP) was measured by competitive enzyme immunoassay. Results:, Cimetidine inhibited both EGF-induced cell proliferation and migration in Hep3B, HLF, SK-Hep-1 and JHH-2, while cimetidine did not affect EGF-induced cell proliferation and migration in PLC/PRF/5 and HLE. Cimetidine was revealed to disrupt the EGF-induced autophosphorylation of EGFR and its downstream effectors, mitogen activated protein kinases and phospholipase C-,. To define the molecular basis of this negative regulation, we identified that cimetidine significantly decreased intracellular cAMP levels and that decrement of cAMP inhibited autophosphorylation of EGFR. The cell permeable cAMP analog, CPT-cAMPS reversed the cimetidine-induced inhibition of EGF-induced cell proliferation and cell migration by restoring autophosphorylation of EGFR. Conclusion:, Cimetidine inhibited EGF-induced cell proliferation and migration in HCC cell lines by decreasing the concentration of intracellular cAMP levels. Cimetidine may be a candidate chemopreventive agent for HCC. [source] Reduced apoptosis in BALB/c mice infected with Heligmosomoides polygyrusPARASITE IMMUNOLOGY, Issue 6 2007M. DOLIGALSKA SUMMARY We evaluated levels of apoptosis and the immune response ex vivo in BALB/c mice infected with Heligmosomoides polygyrus. Cell proliferation, apoptosis and cytokine production were measured in mesenteric lymph nodes (MLN) without exposure to H. polygyrus antigens in culture. The inhibited apoptosis and cytokine production reported might reflect a state of cell hyporesponsiveness in the prepatent phase of infection. These changes were accompanied by changes in the percentage of CD4+ cells in MLN and popliteal lymph nodes (PLN). The prolonged reduction in apoptosis coexisted with induced cell proliferation, elevated TNF-,, IL-12p70, IFN-,, IL-6, IL-10 and TGF-, synthesis, but lowered IL-4 and IL-2 levels. In the chronic phase of infection an increasing production of IFN-,, monocyte chemotactic protein-1 (MCP-1), IL-10 and TGF-, with decreasing concentrations of other cytokines resulted in restored apoptosis. The cytokine response in serum showed moderate production of TNF-,, temporary involvement of IL-12p70, induction of IFN-, and IL-10 synthesis, as well as growing IL-6 and MCP-1 production. It is suggested that a synchronized synthesis of distinct cytokines is accompanied by different levels of inhibited apoptosis during the prepatent and chronic phases of H. polygyrus infection in BALB/c mice. We suggest that immunosuppression provoked by the nematode is not the outcome of parasite-induced apoptosis, but rather results from a hyporesponsiveness experienced by cells during H. polygyrus infection. [source] A role for PSK signaling in wounding and microbial interactions in ArabidopsisPHYSIOLOGIA PLANTARUM, Issue 4 2010Maaria Loivamäki PSK- , is a disulfated peptide that acts as a growth factor in plants. PSK- , is derived from preproproteins which are encoded by five PSK precursor genes in Arabidopsis thaliana (L.) Heynh and is perceived by leucine-rich repeat receptor kinases. Arabidopsis has two PSK receptor genes, PSKR1 and PSKR2. Although ligand and receptor are well characterized, the biological functions of PSK signaling are not well understood. Using reporter lines and receptor knockout mutants of Arabidopsis, a role for PSK signaling in biotic interactions and in wounding was analyzed. Treatment of Arabidopsis leaves with the fungal elicitor E-Fol, or the fungal pathogens Alternaria brassicicola and Sclerotinia sclerotiorum resulted in induction of PSK2 and PSKR1 as shown by promoter:GUS analysis. Wounding of hypocotyls or leaves induced PSK3:GUS, PSK5:GUS and PSKR1:GUS expression indicating that PSK precursor genes are differentially regulated in response to specific stresses. The receptor knockout lines pskr1-3 and pskr2-1 showed significantly reduced photosynthesis in response to the fungal elicitor E-Fol which indicates that fungal defence is impaired. pskr1-3 plants further showed reduced growth of crown galls after infection with Agrobacterium tumefaciens. A role for PSK signaling in Agrobacterium tumefaciens tumor growth was supported by the finding that PSK precursor genes and PSKR1 are expressed in crown galls. Overall, the results indicate that PSK signaling may play a previously undescribed role in pathogen or herbivore interactions and is crucial for Agrobacterium -induced cell proliferation in crown gall formation. [source] Hsp90 mediates insulin-like growth factor 1 and interleukin-1, signaling in an age-dependent manner in equine articular chondrocytesARTHRITIS & RHEUMATISM, Issue 7 2007Amber K. Boehm Objective Many metabolic processes in chondrocytes thought to contribute to age-related changes in the extracellular matrix are influenced by known roles of Hsp90. Age-related decreases in the level of Hsp90 have been documented in numerous cell types and could contribute to cartilage degeneration. The aim of this study was to investigate the roles of age and Hsp90 in insulin-like growth factor 1 (IGF-1) and interleukin-1, (IL-1,) signaling in chondrocytes. Methods Levels of Hsp90 messenger RNA (mRNA) and protein, with respect to age, were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. The Hsp90 inhibitor geldanamycin (50 nM, 100 nM, or 500 nM) was used to assess age-related responses to Hsp90 with concurrent IGF-1 or IL-1, stimulation of chondrocytes. Quantitative real-time PCR was used to measure COL2A1 and matrix metalloproteinase 13 (MMP13) gene expression; Western blot analysis was performed to determine the phosphorylation status of p42/44 and Akt/protein kinase B. Results The effects of Hsp90 inhibition with geldanamycin were concentration dependent. Inhibition of Hsp90 with 100 nM or 500 nM geldanamycin blocked IGF-1,induced cell proliferation, Akt and p42/44 activation, and COL2A1 expression. Basal and IL-1,,induced up-regulation of MMP13 mRNA was blocked by all concentrations of geldanamycin tested. Gain-of-function assays with Hsp90 resulted in increased expression of MMP13 mRNA. Conclusion These results suggest that Hsp90 is involved in opposing signaling pathways of cartilage homeostasis, and that catabolic responses are more sensitive to Hsp90 inhibition than are anabolic responses. Further studies are needed to determine the role of Hsp90 inhibition in osteoarthritis in order to assess its potential as a therapeutic target. [source] Caffeic acid phenethyl ester modulates Helicobacter pylori -induced nuclear factor-kappa B and activator protein-1 expression in gastric epithelial cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2005Mohamed M M Abdel-Latif Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives (honeybee resin), has anti-inflammatory, anti-carcinogenic and anti-bacterial properties. This study was designed to investigate the anti-inflammatory effects of CAPE on Helicobacter pylori -induced NF- ,B and AP-1 in the gastric epithelial cell line AGS. Electrophoretic mobility shift assay was used to measure NF- ,B- and AP-1-DNA binding activity. Western blotting was used to detect I,B- , and COX-2 expression in AGS cells cocultured with H. pylori. The antiproliferative effect of CAPE was measured by MTT assay. Our results showed that caffeic phenethyl ester inhibits H. pylori -induced NF- ,B and AP-1 DNA-binding activity in a dose (0.1,25 ,g ml,1,0.35,88 ,M) and time- (15,240 min) dependent manner in AGS cells. Maximum inhibition by CAPE was observed at concentrations of 25 ,g ml,1 (,88 ,M) CAPE prevented H. pylori - and cytokine-induced degradation of I,B- , protein. Pretreatment of AGS cells with CAPE also blocked cytokine- and mitogen-induced NF- ,B and AP-1 expression. Furthermore, CAPE suppressed H. pylori -induced cell proliferation and production of the cytokines TNF- , and IL-8. In addition, CAPE blocked H. pylori -induced COX-2 expression. The inhibition of such transcription by CAPE could result in suppression of many genes during H. pylori -induced inflammation, and also provide new insights into the anti-cancer and anti-inflammatory properties of CAPE. British Journal of Pharmacology (2005) 146, 1139,1147. doi:10.1038/sj.bjp.0706421 [source] | ||||||||||