共查询到20条相似文献,搜索用时 468 毫秒
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Angeles C. Tecalco-Cruz Marina Macías-Silva Josué Orlando Ramírez-Jarquín Bruno Méndez-Ambrosio 《Biochemistry and Biophysics Reports》2021
Interferon gamma (IFNγ) plays a context-dependent dual tumor-suppressor and pro-tumorigenic roles in cancer. IFNγ induces morphological changes in breast cancer (BC) cells with or without estrogen receptor alpha (ERα) expression. However, IFNγ-regulated genes in BC cells remain unexplored. Here, we performed a cDNA microarray analysis of MCF-7 (ERα+) and MDA-MB-231 (HER2-/PR-/ERα-) cells with and without IFNγ treatment. We identified specific IFNγ?modulated genes in each cell type, and a small group of genes regulated by IFNγ common in both cell types. IFNγ treatment for an extended time mainly repressed gene expression shared by both cell types. Nonetheless, some of these IFNγ-repressed genes were seemingly deregulated in human mammary tumor samples, along with decreased IFNGR1 (an IFNγ receptor) expression. Thus, IFNγ signaling-elicited anti-tumor activities may be mediated by the downregulation of main IFNγ target genes in BC; however, it may be deregulated by the tumor microenvironment in a tumor stage-dependent manner. 相似文献
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CHRK1 encodes a tobacco receptor-like kinase that contains a chitinase-like sequence in the extracellular domain. In a previous study, CHRK1-suppressed transgenic tobacco plants exhibited pleiotropic developmental abnormalities including spontaneous growth of shooty callus from emerging embryos in the absence of any exogenous hormones. In this study, we show that the CHRK1 shooty callus mimics tobacco genetic tumors in its morphology, physiology, and gene expression profiles. Similar to CHRK1 shooty callus, tobacco genetic tumors exhibit shooty callus morphology and hormone-independent shoot organogenesis. Both the CHRK1 callus and genetic tumors constitutively expressed KNOTTED1-type homeobox genes at the high levels, consistent with their vigorous shoot formation. These two types of calli exhibited cell death phenotypes, accompanied by high H2O2 production, increased ion leakage, and callose accumulation. Consistently, both types of calli constitutively expressed high levels of defense genes induced during pathogen-mediated HR cell death. These results, together with previous reports that both the CHRK1 shooty callus and tobacco genetic tumor contained high levels of cytokinin, indicate that CHRK1 shooty callus is a phenocopy of tobacco genetic tumor. CHRK1-mediated signal transduction may play a role in the formation of the genetic tumor in tobacco. 相似文献
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As detailed information accumulates about how cell cycle events are regulated, we can expect new opportunities for application to cancer therapy. The altered expression of oncogenes and tumor suppressor genes that commonly occurs in human cancers may impair the ability of the cells to respond to metabolic perturbations or stress. Impaired cell cycle regulation would make cells vulnerable to pharmacologic intervention by drug regimens tailored to the defects existing in particular tumors. Recent findings that may become applicable to therapy are reviewed, and the possible form of new therapeutic stratagems is considered. 相似文献
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The mechanism of tumor necrosis factor (TNF)-induced cytotoxicity has been investigated using two clonal variants of the ME-180 human cervical carcinoma cell line. The clonal lines were characterized with respect to their expression of TNF receptors, kinetics of cell death, and their ability to communicate intercellularly through gap junctions. The ME-180.4 and ME-180.8 clones were identified by their relative sensitivity to TNF induced lysis in a 24-h assay. The dose of TNF required to kill 50% of the target cells was 60 pM for the sensitive ME-180.4 and 2.5 nM for the ME-180.8. However, when assay times were extended, the dose response for both clones was the same, indicating that a difference in the kinetics of cell death and not absolute TNF sensitivity existed between the ME-180.4 and ME-180.8 clones. Both clones were gap junction deficient as judged by their inability to transfer Lucifer yellow or 6-carboxyfluorescein, a characteristic phenotype of cells sensitive to cytotoxicity by TNF. The level of surface receptor expressed on these clones was nearly identical with a Kd = 0.3 nM and 5,000 binding sites per cell. Measurement of the kinetics of cell death revealed that the time between the addition of TNF and the onset of observed cell death (induction phase) was much shorter for the ME-180.4 (32-55 h) than for the resistant ME-180.8 (55-80 h). Mitomycin C, a DNA alkylating agent, significantly reduced the length of the induction phase for both clones, although the kinetic difference between the clones remained unchanged. Two epipodophyllotoxins, VP-16 and VM-26, which specifically inhibit the rejoining activity of DNA topoisomerase II, showed a 10-100-fold synergistic effect when combined with TNF as shown by isobologram analysis. VM-26 when added to the resistant ME-180.8 clones decreased the length of induction phase and abolished the kinetic difference observed with the ME-180.4 clone. These results indicate that the variance in the TNF response of these two clones was closely associated with DNA topoisomerase II, and suggest that this enzyme may play an important role in TNF mediated cytotoxicity. 相似文献
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Activation—induced cell death in B lymphocytes 总被引:10,自引:2,他引:8
Upon encountering the antigen(Ag),the immune system can either develop a specific immune response of enter a specific state of unresponsiveness,tolerance.The response of B cells to their specific Ag can be activation and proliferation,leading to the immune response,or anergy and activation-induced cell death(AICD),leading to tolerance.AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR).BCR engagement initiates several signaling events such as activation of PLCγ,Ras,and PI3K,which generally speaking,lead to survival.However,in the absence of survival signals(CD40 or IL-4R engagement),BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases,expression of pro-apoptotic genes,and inhibition of pro-survival genes.The complex interplay between survival and death signals determines the B cell fate and, consequently,the immune response. 相似文献
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Toshio Kanno Yuzuru Kubohara Fumio Goto Kuniaki Takata Kensuke Hayashi 《Development, growth & differentiation》2001,43(6):709-716
Differentiation-inducing factor-1 (DIF-1) is a chlorinated alkylphenone (small lipophilic hormone) that induces stalk cell formation in the cellular slime mold Dictyostelium discoideum. Recent studies have revealed that DIF-1 inhibits growth and induces the differentiation of mammalian tumor cells. The present study examines the effects of DIF-1 on rat cortical neurons in primary culture. We found that DIF-1 induced rapid neuronal cell death. The release of lactate dehydrogenase (LDH), as an indicator of cell death, increased dose-dependently with DIF-1. The release of LDH was inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists MK801 and AP5, suggesting that the NMDA receptor is involved in the induction of cell death by DIF-1. However, glutamate cytotoxicity could not explain the entire action of DIF-1 on neurons because the estimated concentration of glutamate around DIF-1-treated neurons was below 50 microM and DIF-1 caused more severe cell death than 500 microM glutamate. We discovered that another portion of DIF-1 cytotoxicity is independent of the NMDA receptor; that is, coaddition of DIF-1 and MK801 induced dendritic beading and increased expression of the immediate early genes c-fos and zif/268. These results indicate that DIF-1 induces rapid cell death via both NMDA receptor-dependent and -independent pathways in rat cortical neurons. 相似文献
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Weihua Li Yanhong Tai Jie Zhou Weiting Gu Zhaofang Bai Tao Zhou Zhijiu Zhong Peter A. McCue Nianli Sang Jun-Yuan Ji Beihua Kong Jie Jiang Chenguang Wang 《Cell cycle (Georgetown, Tex.)》2012,11(12):2348-2358
The aberrantly increased lipogenesis is a universal metabolic feature of proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. SREBP1 and its target genes are overexpressed in a variety of cancers; however, the role of SREBP1 in endometrial cancer is largely unknown. We have screened a cohort of endometrial cancer (EC) specimen for their lipogenic gene expression and observed a significant increase of SREBP1 target gene expression in cancer cells compared with normal endometrium. By using immunohistochemical staining, we confirmed SREBP1 protein overexpression and demonstrated increased nuclear distribution of SREBP1 in EC. In addition, we found that knockdown of SREBP1 expression in EC cells suppressed cell growth, reduced colonigenic capacity and slowed tumor growth in vivo. Furthermore, we observed that knockdown of SREBP1 induced significant cell death in cultured EC cells. Taken together, our results show that SREBP1 is essential for EC cell growth both in vitro and in vivo, suggesting that SREBP1 activity may be a novel therapeutic target for endometrial cancers. 相似文献
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《Cell cycle (Georgetown, Tex.)》2013,12(12):2348-2358
The aberrantly increased lipogenesis is a universal metabolic feature of proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. SREBP1 and its target genes are overexpressed in a variety of cancers; however, the role of SREBP1 in endometrial cancer is largely unknown. We have screened a cohort of endometrial cancer (EC) specimen for their lipogenic gene expression and observed a significant increase of SREBP1 target gene expression in cancer cells compared with normal endometrium. By using immunohistochemical staining, we confirmed SREBP1 protein overexpression and demonstrated increased nuclear distribution of SREBP1 in EC. In addition, we found that knockdown of SREBP1 expression in EC cells suppressed cell growth, reduced colonigenic capacity and slowed tumor growth in vivo. Furthermore, we observed that knockdown of SREBP1 induced significant cell death in cultured EC cells. Taken together, our results show that SREBP1 is essential for EC cell growth both in vitro and in vivo, suggesting that SREBP1 activity may be a novel therapeutic target for endometrial cancers. 相似文献
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Zahra Zandi Bahareh Kashani Davood Bashash Ensieh M. Poursani Seyed A. Mousavi Bahram Chahardoli Seyed H. Ghaffari 《Journal of cellular biochemistry》2020,121(2):1623-1634
Increasing pieces of evidence indicate that inflammatory processes facilitate tumorigenesis; tumor cells simulate the mechanisms by which innate immune cells produce pro-inflammatory cytokines to exploit them for their own survival and proliferation. Toll-like receptor 4 (TLR4), which serves as one of the most well-known receptors on the surface of the immune cells, is often expressed ectopically in the tumor cells resulting in tumor progression, invasion, and chemoresistance. In this study, we examined the anticancer effects of TAK-242, a small molecule inhibitor of TLR4, on different breast cancer cell lines: MCF7, SKBR3, MDA-MB-231, and BT-474. Our results showed that the TLR4 inhibition, as revealed by the downregulation of TLR4 downstream genes, exerted desirable cytotoxicity on the TLR4-expressing cells, at least partly, through the downregulation of EGFR and c-Myc genes. TAK-242 also inhibited the proliferation of anoikis-resistant cells and suppressed the clonal growth of the indicated cells. The results of this study propose a mechanistic pathway by which the inhibition of TLR4 using TAK-242 could augment apoptotic cell death through the alteration of both nuclear factor-кB- and p53-related apoptosis genes in breast cancer cells, especially cells with overexpression of TLR4. Taken together, this study supports the idea that the activation of inflammatory pathways may have a crucial role in breast cancer progression and the inhibition of TLR4 using TAK-242, either as a single agent or in combination, seems to be a novel promising strategy that could be clinically available in foreseeable future. 相似文献
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Monal Patel 《Cell cycle (Georgetown, Tex.)》2018,17(4):506-514
Off-target effects (OTE) are an undesired side effect of RNA interference (RNAi) caused by partial complementarity between the targeting siRNA and mRNAs other than the gene to be silenced. The death receptor CD95 and its ligand CD95L contain multiple sequences that when expressed as either si- or shRNAs kill cancer cells through a defined OTE that targets critical survival genes. Death induced by survival gene elimination (DISE) is characterized by specific morphological changes such as elongated cell shapes, senescence-like enlarged cells, appearance of large intracellular vesicles, release of mitochondrial ROS followed by activation of caspase-2, and induction of a necrotic form of mitotic catastrophe. Using genome-wide shRNA lethality screens with eight different cancer cell lines, we recently identified 651 genes as critical for the survival of cancer cells. To determine whether the toxic shRNAs targeting these 651 genes contained shRNAs that kill cancer cell through DISE rather than by silencing their respective target genes, we tested all shRNAs in the TRC library derived from a subset of these genes targeting tumor suppressors (TS). We now report that only by monitoring the responses of cancer cells following expression of shRNAs derived from these putative TS it was possible to identify DISE-inducing shRNAs in five of the genes. These data indicate that DISE in general is not an undefined toxic response of cells caused by a random OTE but rather a specific cellular response with shared features that points at a specific biological function involving multiple genes in the genome. 相似文献
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We describe a novel genetic screen that is performed by transfecting every individual clone of an expression library into a separate population of cells in a high-throughput mode. The screen allows one to achieve a hitherto unattained sensitivity in expression cloning which was exploited in a first read-out to clone apoptosis-inducing genes. This led to the isolation of several genes whose proteins induce distinct phenotypes of apoptosis in 293T cells. One of the isolated genes is the tumor suppressor cytochrome b(L) (cybL), a component of the respiratory chain complex II, that diminishes the activity of this complex for apoptosis induction. This gene is more efficient and specific for causing cell death than a drug with the same activity. These results suggest further applications, both of the isolated genes and the screen. 相似文献
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The potential of TRAIL for cancer chemotherapy 总被引:5,自引:0,他引:5
Nagane M Huang HJ Cavenee WK 《Apoptosis : an international journal on programmed cell death》2001,6(3):191-197
Innate and acquired resistance to chemotherapy and radiation therapy has been a major obstacle for clinical oncology. One potential adjunct to such conventional treatments is direct induction of cell death by activation of death receptor-mediated apoptosis. TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand), a recently identified member of the growing TNF superfamily, binds to its cognate death receptors DR4 and DR5 as well as decoy receptors DcR1 and DcR2. Upon binding, rapid apoptosis is enacted in a variety of human cancer cell lines independent of p53 status, but not in normal cell lines. TRAIL treatment results in significant growth suppression of TRAIL-sensitive human cancer xenografts in mice. Furthermore, combination treatment of TRAIL with genotoxic chemotherapeutic agents synergistically suppresses growth of tumor xenografts which are otherwise resistant to treatment with TRAIL or chemotherapy alone. Unlike the other death ligands TNF- or FasL, systemic administration of soluble human TRAIL does not cause toxicity in mice and non-human primates. While further studies are needed to evaluate the possible cytotoxicity of TRAIL especially for human hepatocytes, indications are increasing that TRAIL may be a novel therapeutic agent for human cancer. 相似文献
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植物细胞的编程性死亡 总被引:4,自引:1,他引:3
植物细胞受基因调控死亡,这种编程性定位的细胞死亡具有积极的生理功能,形成有利于自身发展的结构。基因调控细胞内的酶活动,细胞器产生变化,导致细胞死亡。外部因素可调节植物基因及基因调控产物的表达。 相似文献