Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathway of growth inhibitory cellular signal transduction by transforming growth factor beta 1 is largely unknown. Although several cellular proteins have been shown to be involved in the pathway, others remain to be identified. To search for other involved proteins, differentially expressed genes were examined in two human hepatoma cell lines that were respectively sensitive and resistant to growth inhibition by TGF-beta 1. Two such genes (SB31 and SB16) were characterized and found to be 100% homologous to leucine-rich alpha 2-glycoprotein and the ribosomal protein S25, respectively. SB31 was coordinately expressed with the TGF-beta I type II receptor, implicating a possible interaction. Expression of both genes in different cell lines can be broadly correlated with the sensitivity of the cell lines to growth inhibition by TGF-beta 1. SB16 expression is strongly suppressed in rat liver regeneration after partial hepatectomy, suggesting that it may have a role in liver growth.
 ...
PMID:Differentially expressed genes in TGF-beta 1 sensitive and resistant human hepatoma cells. 788 5

Close correlation between tissue transglutaminase (tTG) induction and growth regulation and/or cell death processes has been suggested in many cell lineages. In this study, the regulation of the tTG levels by various growth and differentiation factors and its relation to growth rate and cell death processes were investigated in two rat hepatoma cell lines, McA-RH7777 and McA-RH8994, using a monoclonal antibody against liver tTG. Transforming growth factor-beta 1 (TGF-beta 1) and retinoic acid (RA) each increased tTG to the level of 8- to 32-fold above that of control cultures in both cell lines after 72-h treatment. Dexamethasone (DEX) induced a 16- to 32-fold of tTG in McA-RH8994 cells while it did not change the enzyme level in McA-RH7777 cells. Simultaneous addition of DEX and RA increased the tTG level to more than 50-fold in McA-RH7777 cells as well as McA-RH8994 cells. Other factors, such as TGF-alpha, hepatocyte growth factor, dimethyl sulfoxide, and protein kinase C activator, did not show significant increases of the tTG levels. Although tTG induction by TGF-beta 1 or DEX appeared to be correlated with their growth suppressive effects, RA increased the tTG level without suppressing the growth rate of hepatoma cells. TGF-beta 1 was also shown to induce cell death in both cell lines. Our results demonstrate that RA and DEX are capable of modulating the TGF-beta 1-induced cell death processes independent of the tTG levels. We present evidence here that tTG induction by itself is not the direct cause of growth suppression and cell death in these hepatoma cells.
 ...
PMID:Differential regulation of tissue transglutaminase in rat hepatoma cell lines McA-RH7777 and McA-RH8994: relation to growth rate and cell death. 790 35

The basic approach in targeted gene delivery relies on the formation of a complex between a vector and a molecule that will be selectively internalized by the target cells. In the case of hepatocytes, asialoglycoproteins are convenient targeting molecules because of the high affinity and avidity of the hepatocyte galactose receptor. In this system, poly-L-lysine is cross-linked to an asialoglycoprotein, and the resulting conjugate is complexed with the expression vector (DNA). The electrostatic binding between DNA and poly-L-lysine-asialoglycoprotein ensures delivery of the intravenously injected complex to the liver, where it is subjected to endocytosis by hepatocytes. However, the poly-L-lysine-asialoglycoprotein complexes tend to be unstable, of limited solubility and of fixed carbohydrate content. For these reasons we searched for a simpler alternative. We exploited the known capacity of reducing sugars to be reductively coupled to the epsilon-amino groups in proteins and used lactose to obtain poly-L-lysine with "exposed" galactose. Glycosylation with sodium cyanoborohydride at high pH in borate buffer is a simple, reproducible procedure. The "lactosylated" poly-L-lysine has proved very stable, highly soluble and easily bound to plasmids. In a set of experiments we compared the asialofetuin-poly-L-lysine vector complexes with lactosylated poly-L-lysine vector complexes by transfecting hepatoma cells (HepG2) in culture. For these experiments we used a pRc/cytomegalovirus eukaryotic expression vector containing a mutant TGF-beta 1 complementary DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nonenzymatic glycosylation of poly-L-lysine: a new tool for targeted gene delivery. 798 61

Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme-linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF-alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.
 ...
PMID:Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG-2 hepatoma cell line. 802 76

Apoptotic cell death plays a major role in the regulation of cell growth and this process may be activated by different agents through various pathways. The present study aimed to elucidated the mechanism of apoptosis caused by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cells. Several biological parameters which were reported to be crucial in the induction of programmed cell death in other experimental systems were measured. We found that TGF-beta 1-induced cell death is independent of cytosolic calcium and protein kinase C. Insulin and tumor promotor can rescue hepatoma cells from apoptosis, but the effect is time-dependent. Our results highlight that different apoptotic signal transduction pathways exist in different cell types. Apoptosis induced by TGF-beta 1 provides a good model for the understanding of cell death and the development of new anti-cancer drugs. Apoptotic cell death (apoptosis or programmed cell death) in normal tissue is a biological phenomenon that maintains hemostasis of systems of the body under physiological conditions. The features of apoptosis include condensation of chromatin, blebbing of the cell surface, transient increase in buoyant density and fragmentation of chromatin by a specific endonuclease.
 ...
PMID:Characterization of apoptosis induced by transforming growth factor beta 1 in human hepatoma cells. 816 42

In patients with the anemia of chronic diseases, the plasma level of EPO is often low in relation to the blood hemoglobin concentration. Because infectious and inflammatory processes cause activation of cytokine-producing macrophages and lymphocytes, we investigated whether isolated inflammatory cytokines influence the synthesis of EPO in vitro. IL-1 and TNF-alpha were shown to inhibit EPO mRNA levels and EPO formation in the human hepatoma cell cultures HepG2 and Hep3B, and to lower EPO formation in isolated perfused rat kidneys. IFN-alpha and IFN-beta also induced some inhibition of EPO production in HepG2 cultures. IL-3, TGF-beta 2, and IFN-gamma did not inhibit. IL-6 stimulated the production of EPO in Hep3B cells but was ineffective in HepG2 cells and lowered EPO production in isolated perfused rat kidneys. IL-1, TNF-alpha, and possibly other cytokines could contribute to defective EPO production in renal and nonrenal immune responses.
 ...
PMID:Inhibition of erythropoietin production by cytokines. Implications for the anemia involved in inflammatory states. 818 37

A culture model for invasion of rat mesothelial cell layer by rat ascites hepatoma cells has been developed. By using this quantitative model, we have recently found that the invasiveness of tumor cells is not only genetically determined but is greatly influenced by their interactions with host cells and host mediators. The preculture with macrophages was found to enhance both the in vitro and in vivo invasive potentials of the tumor cells. This potentiation appears to be mediated partly by oxygen radicals generated by the cocultured macrophages. The in vitro invasive capacity was also augmented by pretreating the tumor cells with TGF-beta, or with activated platelets. In the in vitro invasion assay system, tumor cells did not invade against cultured mesothelial cell monolayers without fetal calf serum. Serum could be completely substituted by oleoyl-lysophosphatidic acid (LPA) or bacterial phospholipase D (PLD), suggesting a possible participation of particular signaling cascade, PLD-LPA(PA) system, in the invasion of certain tumor cells.
 ...
PMID:[Mechanism of tumor cell invasion studied by a culture model--modification of invasiveness by host mediators]. 829 16

The biological activity of many cytokines is regulated by binding proteins present at the cell surface, in extracellular matrices or in soluble phase. We describe here a TGF-beta binding protein that is both an extracellular matrix and a cell surface protein. When intact extracellular matrices of HEP-G2 cells were affinity cross-linked with 125I-TGF-beta 1, two major binding components were seen: a 250-kD, proteoglycan-like molecule, presumed to be betaglycan, and a 60-kD protein. The 60-kD TGF-beta-binding protein was also present at the cell surface. It could be released from the cell surface by treating cells with high salt, heparin, chondroitin sulfate, heparitinase, or chondroitinase, indicating that it is bound to heparan sulfate and chondroitin sulfate proteoglycans. The 60-kD protein bound TGF-beta 1 with an apparent dissociation constant of 1.6 nM, and there were 30,000 binding sites per cell at the cell surface. In addition to the HEP-G2 cells and another hepatoma cell line, the 60-kD protein was also found in a human colon carcinoma (HT-29) cell line but not in rat kidney (NRK-49F) or human fibroblast (HUT-12) cell lines. The 60-kD protein could be extracted from cells containing it and transferred to the surface of previously negative cells. The 60-kD protein may serve to regulate the binding of TGF-beta to its signal transducing receptors by targeting TGF-beta to appropriate locations in the microenvironment of cells.
 ...
PMID:A 60-kD protein mediates the binding of transforming growth factor-beta to cell surface and extracellular matrix proteoglycans. 833 95

The growth of human hepatoma Hep 3B cells is potently inhibited by TGF-beta 1 (ID50 = 0.2 ng/ml, 8 pM). A mutant cell line was derived that was not inhibited in growth by TGF-beta 1 at 5 ng/ml (200 pM) and that lacked TGF-beta receptor type II (TGF-beta RII) gene. Transfection of the cloned cDNA for human TGF-beta RII to this mutant cell line restored receptor expression as well as the inhibition in growth by TGF-beta 1. In both wild-type and mutant cells stably transfected with TGF-beta RII cDNA, TGF-beta RII coimmunoprecipitated with TGF-beta receptor type I in the presence of ligand. These experiments provide direct evidence for the role of TGF-beta RII in the inhibitory effect of TGF-beta on growth and suggest that TGF-beta RII acts by means of a heteromeric surface complex with TGF-beta receptor type I.
 ...
PMID:Growth inhibition by transforming growth factor beta (TGF-beta) type I is restored in TGF-beta-resistant hepatoma cells after expression of TGF-beta receptor type II cDNA. 838 83

The effects of insulin on cell growth control by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cell lines were studied. TGF-beta 1 inhibited cell growth and DNA synthesis of Hep3B cells but not that of HA22T/VGH cells. The cell cycle-dependent p34cdc2 kinase activity was inhibited by TGF-beta 1 in a dose-dependent manner in Hep3B cells. In contrast, the p34cdc2 kinase activity of HA22T/VGH cells was not regulated by TGF-beta 1. When insulin (10(-7) M) was added simultaneously with TGF-beta 1, we found that the inhibitory effects of TGF-beta 1 on cell growth and DNA synthesis in Hep3B cells was completely blocked and the p34cdc2 kinase activity of Hep3B cells was recovered after insulin administration. Thus, cell growth inhibition by TGF-beta 1 in Hep3B hepatoma cells can be antagonized by insulin and their interaction may play an important role in the tumor progression stage of hepatocarcinogenesis.
 ...
PMID:Effects of insulin on TGF-beta 1-induced cell growth inhibition in the human hepatoma cell lines. 840 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>