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1.
Ubiquitination and deubiquitination are important mechanisms for regulating cell signal transduction. They regulate target proteins precisely and participate in physiological and pathological processes such as growth, development, immune response and cancer. OTUD7B (OTU domain-containing 7B) is a deubiquitinase that hydrolyzes K11-, K48- and K63-linked polyubiquitin chains, regulates intracellular signal transduction and mediates cell survival and proliferation. The abnormal expression of OTUD7B in various malignant tumors affects tumor progression and immune microenvironment. Here, we reviewed OTUD7B-mediated cellular signal transduction and its role in malignant tumors, in order to provide clues for the discovery of new targets of anti-cancer therapy targeting ubiquitin system. 相似文献
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AIM: To explore the effect and significance of neuregulins /ErbB2 receptor signal transduction pathway on mtp53 and hypoxia-iducible factor-1α (HIF-1α) in none-overexpression ErbB2 breast cancer cell MDA-MB-231. METHODS: The expression of neuregulin was detected by immunocytochemistry and Western blotting. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferation was measured by MTT assay. The cell cycle and apoptosis were determined by flow cytometry. The expressions of mtp53 and HIF-1α were detected by Western blotting. The mRNA expression of HIF-1α was detected by RT-PCR. RESULTS: MDA-MB-231 cells expressed a relative higher level of neuregulin. In the results of Western blotting, the positive reaction band was found in 44 kD which coincides with the molecular weight of neuregulin. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in time and dose dependent manners (P<0.01). The cell cycle was arrested in G0/G1 phase (P<0.05). The apoptosis rate was increased (P<0.05). The protein expression levels of mtp53 and HIF-1α were decreased (P<0.05), and the mRNA level of HIF-1α was also decreased (P<0.05).CONCLUSION: Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins. Neuregulins activate ErbB2 receptor signal transduction pathway by ligand autocrine or paracrine actions, and play an important role in proliferation of none-overexpression ErbB2 breast cancer cell MDA-MB-231. Proliferation and survivorship, and inhibition apoptosis can be induced with up-regulation of mtp53 and HIF-1α level. 相似文献
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AIM:To explore the signal transduction pathways of calcium-sensing receptor(CaSR) that mediates hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells(PASMCs). METHODS:The expression of cyclin D1 and phosphorylated protein kinase B(p-Akt) was analyzed by Western blotting. Cell proliferation was tested using a BrdU incorporation assay, and cell cycle analysis was carried out using a flow cytometric assay. RESULTS:Hypoxia significantly increased the expression of cyclin D1 and p-Akt, the BrdU incorporation and the cell proliferation index. GdCl3, an agonist of CaSR, amplified the effect of hypoxia. LY294002,a PI3K inhibitor, decreased the up-regulation of cyclin D1 expression and the BrdU incorporation, and also inhibited the increase in the cell proliferation index induced by hypoxia and GdCl3 in PASMCs. CONCLUSION: The CaSR mediates hypoxia-induced proliferation of rat PASMCs through PI3K pathways. 相似文献
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AIM: To explore the effect of collagen and C-erbB-2 protein on the adhesion and the proliferation in hepatocellular carcinoma cells. METHODS: Hepatocellular carcinoma cell line (HepG-2) identified to positive for C-erbB-2 gene was used to study the adhesion and the growth feature by the action of rat tail collagen and C-erbB-2 antibody.RESULTS: The action of rat tail collagen to potentiated the adhesion in HepG-2 cells was significantly but no proliferation effect was observed. C-erbB-2 antibody inhibited the adhesion and proliferation of HepG-2 cells and also abolished the potentiated effect of rat tail collagen on the adhesion in HepG- 2 cells. CONCLUSION: The signaling transduction mediated by C-erbB-2 protein was correlated to the adhesion and the proliferation of HepG-2. The blockage of C-erbB-2 gene signal transduction may be a strategic target to the treatment of liver cancer in the future. 相似文献
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Erythropoietin-producing hepatocyte (Eph) receptor, a membrane-bound protein tyrosine kinase receptor, plays the function of bidirectional signal transduction by binding to the membrane-tethered ephrin ligands on the neighboring cells. New findings reveal that Eph-ephrin bidirectional transduction of signals plays roles in embryonic deve-lopment and the physiological metabolism of adult organs, and its dysfunction is involved in a variety of pathological processes, such as cell adhesion and separation, angiogenesis, nerve growth and remodeling, bone remodeling, tumorigenesis and development, immune and metabolic diseases. Therefore, in-depth study of Eph-ephrin is of great significance for understanding the pathophysiological mechanisms and treatment of diseases. This review discusses the progress in Eph-ephrin bidirectional signal transduction system. 相似文献
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AIM:To investigate the crosstalk between angiotensin Ⅱ (AngⅡ)-mediated and platelet-derived growth factor (PDGF)-mediated signal transduction in vascular smooth muscle proliferation.METHODS:A model of renal hypertension was made by two kidney/one-clip operation. Level of PDGF receptor β subunit of aorta was measured by Western Blot analysis. The effect of Ang Ⅱ on PDGF receptor β subunit expression was investigated in culture rat aortic vascular smooth muscle cells (VSMC).RESULTS:Systolic blood pressure obviously increased at 8th week after operation, whereas the level of PDGF receptor β subunit of aorta significantly increased by 126.6% (P＜0.05) in 2K1C rats compared with control group. The expression of PDGF receptor β subunit in cultured VSMC stimulated by AngⅡ was higher than that of control by 192.74%(P＜0.01). The effect of AngⅡ was inhibited remarkably by pretreated with losartan, a kind of specific AngⅡ receptor 1 (AT1) subtype antagonist and U73122, a kind of phospholipase C inhibitor. The effect was partly blocked by PD98059, which inhibit the activity of mitogen-activated, ERK-activating kinase (MEK).CONCLUSION:AngⅡ-induced PDGF receptor β subunit expression is regulated by the AT1 and its downstream signal molecule-PLC and ERK, might participate in the intracellular signal transduction pathway. 相似文献
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AIM: To evaluate the effect of bFGF on the apoptosis and the expression of glucose regulated protein 78 (GRP78) in ovarian cancer CAOV3 cells.METHODS: Starvation induced cell apoptosis was conducted. After treatment with bFGF, the cell cycle and apoptosis were determined by FACS analysis and Annexin V/PI staining, respectively. The expression of protein kinase B (PKB) and GRP78 were detected by Western blotting and RT-PCR. RESULTS: Compared to starvation group, the cells treated with bFGF were still viable and increased activation of PKB and high expression of GRP78 were observed, which were prevented by PKB inhibitor wortmannin effectively (P<0.01). CONCLUSION: bFGF plays a critical role in anti-apoptosis and proliferation in human ovarian cancer through PKB signal transduction pathway, partly by upregulating the expression of GRP78. 相似文献
8.
XU Ruo-bing WEN Jian-ming ZHANG Meng LV Chang-hai XIAO Gang ZHANG Wen-min LIANG Hui-zhen 《园艺学报》2004,20(11):1982-1988
AIM: To study effects of urokinase-type plasminogen activator (uPA) signal transduction on expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) in giant cell tumor of bone (GCT). METHODS: Expression of uPAR, MMP-2 and TIMP-3 in GCT tissue was detected by immunohistochemistry. Phosphorylation level of mitogen-activated protein kinase (p44) in uPA/uPAR signal pathway in cultured GCT cells was detected by immunoprecipitation. The expression of MMP-2 and TIMP-3 in cultured cells after treatment with uPA-ATF or anti-uPAR antibody was also detected by Western blotting. RESULTS: 1) Urokinase-type plasminogen activator receptor (uPAR) was positive on the cell membrane and in cytoplasm of some mononuclear stromal cells (MSCs) and multinucleated giant cells (MGCs); 2) MMP-2 was positive in the cytoplasm and on the cell membrane of almost all of MSCs and some of MGCs. The polar distribution of MMP-2 in the cytoplasm of MGCs was especially obvious; 3) The expression of TIMP-3 of some MSCs and MGCs in GCT was much lower than MMP-2. The positive signal also showed a prominent polarity; 4) After treatment with uPA-ATF, the phosphorylation level of p44 in GCT cultured cells was much higher than the control. Addition of anti-uPAR antibody in the cells remarkably down-regulated the phosphorylation level of p44 as compared with the control group, suggesting that uPA-ATF participates cell signal transduction and this reaction can be inhibited by anti-uPAR antibody; 5) uPA-ATF cell signal pathway up-regulated expression of MMP-2 and TIMP-3, while anti-uPAR antibody down-regulated the expression of MMP-2 and TIMP-3. CONCLUSION: These results demonstrate for the first time that uPA-ATF directly regulates the expression of MMP-2 and TIMP-3 by signal transduction pathway, and the over-expression of MMP-2 and TIMP-3 may play an important role in local osteolysis of GCT. 相似文献
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AIM: To detect the differentially expressed genes associated with ovarian serous cystadenocarcinoma (OV) by microarray and to analyze the participated signaling pathway. METHODS: We analyzed 16 datasets of Affymetrix GeneChip Human Exon 1.0 ST Arrays from The Cancer Genome Atlas (TCGA), including 8 OV and 8 normal ovary samples. The function of differential genes was determined by pathway and gene ontology (GO) analysis. The probable functions of the key genes were predicted according to intergenic signal transduction network. RESULTS: The 1 144 genes were identified as distinctively expressed in OV (P<0.05), 747 of which were up-regulated and 397 were down-regulated. The GO analysis results showed that the altered genes were involved in 362 up-regulated and 160 down-regulated significant functions (P<0.05) related to cell cycle, DNA replication, cell proliferation, cell apoptosis, cell adhesion, etc. The pathways of the different genes were involved in the 59 enrichment-related pathways (P<0.05), 45 of which were up-regulated and 14 were down-regulated. Among the 59 pathways, cell cycle, P53 signaling pathway, DNA replication, pathways in cancer, PI3K-Akt signaling pathway, ECM-receptor signaling pathway, cell adhesion molecules and cell apoptosis were related to tumor genesis, development and metastasis. As a result, 229 genes with significant functions and pathways in GO and pathway analysis were selected to construct signal transduction network (Signal-Net), 4 of which, CDK1, PLK1, MCM3 and PGK1, were found to play key roles in OV signal regulation network. CONCLUSION: The OV shows abundant differentially expressed genes that play key roles in cancer-related signal pathways. 相似文献
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IL-13 is a pleiotropic cytokine mainly secreted by activated Th2 cells. It has 2 receptors, IL-13Rα1 and IL-13Rα2. The latter had been thought to serve exclusively as a decoy receptor for a long period of time due to its short cytoplasmic tail and lack of signal transduction structure. Since Fichtner-Feigl reported in Nature Medicine that IL-13 is involved in induction of TGF-β production and tissue fibrosis through IL-13Rα2-mediated signaling pathway, it was found that IL-13Rα2 has more sophisticated functions than just a simple decoy receptor as more and more researches have explored its signaling functions. This review combines the most advanced research results with previous investigation and discusses the gene structure, expression, production, distribution, subtype conversion and possible signal pathways mediated by this receptor. More importantly, the connection with human diseases and the applications in disease diagnosis and molecule targeted therapy for cancer are also discussed. 相似文献
11.
The renin-angiotension system (RAS) plays an important role in cardiovascular and renal physiology and diseases. Recent discoveries of prorenin and prorenin receptor add new contents to RAS. Renin and prorenin binding to the prorenin receptor not only target and facilitate angiotensin generation but also lead to activation of prorenin receptor signal transduction pathways, which is distinct from classical RAS signaling. In this paper, the construction, function and signal trasduction of prorenin, prorenin receptor and handle region peptide are reviewed. 相似文献
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AIM: To evaluate the relationship between cell proliferation, DNA proliferative fraction (S+G2/M), DNA ploidy, biological features and survival in gastric cancer patients. METHODS: Proliferation, DNA proliferative fraction and DNA ploidy were analyzed by flow cytometry using standard techniques. RESULTS: No correlation between proliferation and DNA proliferative fraction (P>0.05) was observed. Likewise, there was no correlation between proliferation, DNA proliferative fraction and survival (P>0.05), nor was there a difference between proliferation, DNA ploidy and clinical pathological variables (P>0.05). Using Kaplan-Meier survival curves and the Log-rank test, statistic difference was found in patients with DNA diploid tumors and those with DNA aneuploid tumors (P<0.05). CONCLUSION: Proliferation and DNA proliferative fraction in gastric cancer do not appear to correlate with survival, but DNA ploidy can be used as a prognostic factor in gastric cancer. 相似文献
14.
AIM: In order to study the effect of the extracellular domain of cadherin 5 on the growth of a human breast cancer cell line MDA-MB435.METHODS: Cadherin extracellular domain repeats 1 to 4(CED1-4) was cloned by using RT-PCR technique,and inserted into the plasmid vector pMSCV.pMSCV-CED1-4 was propagated in XL-blue strain of Escherichia coli,extracted and purified.CED1-4 was cut by restriction endonuclease,examined by using agar gel electrophoresis,and finally sequenced.CED1-4 gene was transferred into MDA-MB435 cell line.The expression of CED1-4 gene in MDA-MB435 cell was analyzed by methods of RT-PCR and Western blotting.The effect of CED1-4 on the growth of MDA-MB435 cell was observed by the methods of proliferation experiments in vitro and the experiments in nude mice in vivo.RESULTS: The recombinant vector pMSCV-CED1-4 was successfully constructed.CED1-4 band appeared between the 1 636 bp and 1 018 bp in agar gel electrophoresis.The sequence result showed that CED1-4 had 1 452 bp and codes 484 amino acids.PCR and Western blotting identified that CED1-4 mRNA and protein were expressed in the transfected MDA-MB435 cells.Cell proliferation experiments showed that the proliferation rate of MDA-MB435 cells was lower in the experimental group than that in the experimental control group and the blank control group.The mean volume and weight of tumors in nude mice were lower in the experimental group than those in the experimental control group and the blank control group.CONCLUSION: The growth of a human breast cancer cell line MDA-MB435 is inhibited in vitro and in vivo by cadherin 5 extracellular domain CED1-4. 相似文献
15.
AIM: To study the role of androgen receptor (AR) in hormone-dependent and hormone-independent prostate cancer cell proliferation by knocking down AR expression with adenovirus-delivered siRNA. METHODS: Four well-designed siRNAs were synthesized and inserted into the adenovirus plasmid pShuttle-H1-Ri. The recombinant pShuttle-H1-Ri-AR plasmid was then co-transfected with pcDNA-AR to HEK293 cell line and Western blot was used to detect the inhibitory efficiency of different siRNAs on AR expression. Recombinant adenovirus containing more efficient siRNAs were prepared and used to infect three different humane prostate cancer cell lines including LNCap、C4-2B and CWR22Rv1. The efficiency of knocking down AR expression was detected by Western blot. The effect of AR-knocking down on cell proliferation was detected by MTT colorimetric assay. RESULTS: All of the four designed siRNAs could knock down AR expression in transient co-transfection. Infecting with recombinant adenovirus containing more efficient siRNAs in hormone-dependent and hormone-independent prostate cancer cell lines specifically knocked down AR expression with high efficiency. Knocking down AR expression significantly decreased the proliferation rate in all these prostate cancer cells. CONCLUSION: The suppressed expression of AR in prostate cell lines mediated by siRNA could efficiently inhibit the cell proliferation, and these results show that AR plays an important role in the proliferation of hormone-dependent and hormone-independent prostate cancer cells. AR is an important therapeutic target for the treatment of prostate cancer. 相似文献
16.
AIM: To investigate the therapeutic action of secreted endostatin (ES) on breast cancer cells. METHODS: Retroviral-mediated endostatin gene was transferred to breast cancer cell line MDA-MB-231. The ES biological properties and function were evaluated by polymerase chain reaction (PCR), MTT and a murine xenograft model. RESULTS: After retroviral transduction, endostatin genetically modified breast tumor cells were confirmed by PCR, and the integration and durative expression of endostatin gene was successfully committed. Compared with controls, endostatin secreted by genetically modified cells markedly inhibited endothelial cell proliferation (P<0.05) while the influences on the growth of MDA-MB-231 cell line in vitro were not found (P>0.05). The results of the transplanted subcutaneous tumor model in nude mice suggested that the subcutaneous growth of MDA-MB-231 was significantly inhibited by the expression of endostatin gene (P<0.05). In experimental groups, the tumor microvascular density (MVD) and VEGF expression were decreased. CONCLUSION: Retroviral- mediated overexpression of endostatin inhibits the proliferation of vascular endothelial cells and angiogenesis that associated with tumor growth in vivo via the paracrine pathway, which has a potential effect in the angiostatic gene therapy for breast cancer. 相似文献
17.
AIM: To investigate the relationship between high density lipoprotein (HDL) subclasses and the binding activities of hepatic cell and extra-hepatic cell HDL receptor and intracellular protein kinase C (PKC). METHODS: Using purified pre-β1 HDL and apoE-deficent HDL3 to react with human smooth muscle cells (SMC) and HepG2 cells, then the activities of pre-β1HDL and apoE-deficent HDL3 binding to SMC and HepG2 cells, and the effects of this two HDL subclasses on PKC activities in SMC and HepG2 cells were observed . RESULTS: The results showed that the value of Kd of pre-β1HDL binding to SMC HDL receptor was not only significantly lower than that of apoE-deficient HDL3 (P<0.05), but significantly lower than pre-β1 HDL binding to HepG2 HDL receptor (P<0.05). Cell PKC system was all activated by binding of the two HDL subclasses with SMC HDL receptor, and the effect of pre-β1HDL appeared to be stronger than apoE-deficent HDL3. No change in HepG2 cell PKC activity by binding the two HDL subclasses with HepG2 HDL receptor was observed. CONCLUSIONS: The results indicate that the ability of pre-β1HDL to promote efflux of cholesterol from extra-hepatic cells is stronger than that of apoE-deficent HDL3, and it seems that plasma pre-β1 HDL mainly interacts with extra-hepatic cell HDL receptor, subsequently, activates PKC signal transduction system and promotes the intracellular cholesterol efflux from cells. 相似文献
18.
AIM:To study the effects of genistein on JAR/MTX cell proliferation, apoptosis and invasion and it's mechanism in vitro. METHODS:MTT assay, Annexin-Ⅴ and propidium iodide label analysis and invasion assay were used to determine the effects of genistein on proliferation, apoptosis and invasiveness in JAR/MTX methotrexate- resistant human choriocarcinoma cells. RT-PCR was used to estimate the relative mRNA amounts of estrogen receptor(ER), MTA3 and snail in the cells. Western blotting and gelatin zymography assay were used to estimate the relative protein amounts of MMP-2, MMP-9 and E-cadherin in the cells. RESULTS:After treatment of genistein, the proliferation and invasiveness of JAR/MTX cells were decreased significantly in a dose-dependent manner. 10 μmol/L genistein induced apoptosis, whereas 25, 50, 100 μmol/L genistein induced apoptosis and necrosis significantly. Genistein led to an increase in ERβ, MTA3 mRNA and E-cadherin protein expression, and decreases in the amounts for snail mRNA and MMP-2 and MMP-9 protein expression of JAR/MTX cells. CONCLUSIONS:Genistein inhibits the cell proliferation by inducing cell apoptosis and necrosis. Genistein also may inhibit JAR/MTX cell invasion in part through the upregulation of E-cadherin and downregulation of MMP-2 and MMP-9. The signal transduction pathway of invasion suppression induced by genistein in JAR/MTX cells may be as follows: MTA3→snail→ E-cadherin. 相似文献
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CD69, a member of C type lectin superfamily and NK cell gene family, plays important roles in signal transduction in the regulation of cellular functions. Previous studies demonstrate that CD69 has a vital role in cell activation and CD69 is used as a marker of cell activation because of its early expression in activated cells. CD69 is also the costimulatory signal for cell activation, proliferation and differentiation. Furthermore, recent studies show the close association between CD69 and apoptosis. CD69 mediates apoptosis selectively in activated cells, mainly in activated eosinophils and monocytes. Using CD69 as an apoptotic inducer in certain cells may have good result and less side effect. This article tries provide a brief summary of the dual immunoregulatory effects of CD69 on cell activation and apoptosis. 相似文献
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Caveolae are vesicular invaginations in the plasma membrane,caveolin-1 is the marker protein of caveolae.Recently,much attention has been paid to the functions of caveolae/caveolin-1.Studies show that the disorders of cellular cholesterol homeostasis participate in the development of atherosclerosis.Meanwhile,caveolar/caveolin-1 play a critical role in the regulation of cellular cholesterol transport and homeostasis,cell proliferation and migration,signal transduction and tumor suppression and so on.In this review,we provide an in-depth summary regarding the research development of caveolae/caveolin-1 and cellular cholesterol transport. 相似文献