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

Signal Transducer and Activator of Transcription 3 (Stat3) is a latent protein activated in response to various cytokines and growth factors. It is believed that Stat3 is a key signaling molecule involved in the regulation of acute phase gene expression by interleukin 6 (IL-6) in hepatocytes. We report that both IL-6 and interferon gamma (IFN gamma) up-regulate the expression of Stat3 on both mRNA and protein levels in rat and human hepatoma cells. The effect of IL-6 and IFN gamma on Stat3 mRNA expression was time- and dose-dependent. Other factors, including IL-1, TNF alpha, EGF, Dexamethasone and PMA, did not have any effect on Stat3 mRNA expression. Moreover, we show that the rapid induction of Stat3 expression by IL-6 and IFN gamma was independent of ongoing protein synthesis, suggesting regulation by Stat3 and Stat1, respectively.
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PMID:Activation of signal transducer and activator of transcription-3 (Stat3) expression by interferon-gamma and interleukin-6 in hepatoma cells. 748 23

The growth characteristics of a newly established cell line, Hep40, derived from a human hepatoma are described. An absolute requirement was found for serum to mediate cell growth. Neither EGF, TGF-alpha, nor HGF altered cell growth in the presence or absence of serum. A partial suppression of cell growth was achieved by several TGF-beta family proteins. Affinity crosslinking gels using 125I-labeled TGF-beta showed a significant decrease in the TGF-beta cell-surface type II receptor in Hep40 cells, compared to the TGF-beta-sensitive Hep3B cell line. However, growth could be completely suppressed by addition of vitamins K to the culture medium in both Hep40 and several other hepatoma cell lines. Growth suppression by vitamins K was accompanied by an increased level of transcripts for c-myc, c-jun, and prothrombin genes, in contrast to the actions of TGF-beta 1 protein, which caused a decrease in the level of c-myc transcripts. These data show that this new human hepatoma cell line has partial resistance to growth inhibition by TGF-beta with a unique TGF-beta receptor defect. However, growth was completely suppressed by vitamins K. The differing gene expression patterns in response to TGF-beta as compared to vitamin K suggest that these two growth inhibitors act through differing pathways.
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PMID:Growth control and gene expression in a new hepatocellular carcinoma cell line, Hep40: inhibitory actions of vitamin K. 759 24

Single and double immunohistochemical staining for transforming growth factor (TGF)-alpha and epidermal growth factor-receptor (EGF-R) was done in order to identify the localization of TGF-alpha and EGF-R in human hepatocellular carcinoma (HCC). Single immunohistochemical staining for TGF-alpha showed immunoreactivity in the cytoplasm of hepatoma cells in 22 of 30 cases of HCC. The localization of TGF-alpha was heterogeneous from HCC cells to HCC cells. In the surrounding regenerative nodules, the hepatocytes were mildly to moderately positive for TGF-alpha. The proliferating bile ductules and peripheral nerves were also immunopositive for TGF-alpha. Single immunohistochemical staining for EGF-R demonstrated a linear localization of EGF-R along the cell membrane of the HCC cells in 21 of the 30 cases of HCC. In the regenerative nodules, the hepatocytes also showed linear staining along the cell membrane. Double staining for TGF-alpha and EGF-R in 12 cases of HCC showed a concurrent localization of TGF-alpha and EGF-R in some hepatoma cells and isolated localization of the two substances of other HCC cells. These combinations either abruptly moved around or intermingled with each other. These immunohistochemical results thus support the theory of an autocrine, paracrine, and endocrine mechanism of TGF-alpha and EGF-R on the proliferation of human hepatocellular carcinoma.
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PMID:Concomitant and isolated expression of TGF-alpha and EGF-R in human hepatoma cells supports the hypothesis of autocrine, paracrine, and endocrine growth of human hepatoma. 772 67

In order to get a better understanding of expressions of multiple oncogenes and their possible roles in human hepatocarcinogenesis, 379 cases of liver tissues were investigated immunohistochemically. EGF receptors were immunolocalized mainly in the sinusoidal endothelial cells. They might not take part in the development of hepatocellular carcinoma (HCC), c-myc protein was showed to be expressed in cancer cells and the hepatocytes in the so-called "large-cell dysplasia" and in ductular metaplasia (DM). Its expression was also observed in some zone II hepatocytes of hepatic accini in 21% of normal liver tissues, which indicated that c-myc expression might also be related to the proliferation of mature hepatocytes. The positivity rate of c-erbB-2 product was shown to be highest among the oncogenic genes examined in this study. The positivity was observed in small polygonal liver cells (SPLCs) and the hepatocytes were observed in SCD and in DM. The expression level of c-erbB-2 oncogene in HCC cells was higher significantly than in normal hepatocytes, but lower than in SPLCs, the hepatocytes in SCD and in DM. We suggest that c-erbB-2 gene activation may play an important role not only in HCC genesis, but also in DM. Insulin-like growth factor II (IGF II), an oncofetal hepatocellular growth factor, was immunolocalized in the cancer cells, SPLCs and the hepatocytes in SCD, which indicated that activation and hyperexpression of IGF II gene might be responsible for the prominent proliferation of SPLCs and SCD, a crucial step in malignant transformation of hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Expression of c-myc, c-erbB-2, insulin-like growth factor II andepidermal growth factor receptor in hepatitis B, cirrhosis and hepatocellular carcinoma]. 778 Aug 18

The rat liver ectoATPase has reportedly been cloned. The cDNA, a member of the carcinoembryonic antigen (CEA) gene family, was shown to increase aggregation of transfected cells, but ATPase activity was not evaluated. Using this cDNA as a probe to clone the mercurial-insensitive ectoATPase (MI-ectoATPase) of human hepatoma Li-7A cells, the cDNA obtained was that of CEA which has no ATPase activity. The probe also did not detect increased transcription when MI-ectoATPase activity was induced in Li-7A cells. It is concluded that the "rat liver ectoATPase cDNA" codes for a cell adhesion molecule but does not code for an ectoATPase. It was also discovered that expression of four CEA transcripts in Li-7A cells was markedly stimulated by a single growth modulator, EGF, and was further stimulated by a cAMP elevating agent, cholera toxin.
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PMID:The rat liver ecto-ATPase/C-CAM cDNA detects induction of carcinoembryonic antigen but not the mercurial-insensitive ecto-ATPase in human hepatoma Li-7A cells treated by epidermal growth factor and cholera toxin. 786 39

The expression of PCNA and EGF gamma in chemically induced hepatocellular carcinoma and squamous cell carcinoma cells from rats were observed with immunohistochemical techniques. The results showed that the carcinoma cells of both tumors revealed a positive immunoreaction to both factors. According to the amount of MC surrounding the tumor cell nests, the specimens could be divided into two groups: the group with abundant MC infiltration and the group with little or no MC infiltration. The PCNA positive cells in carcinoma cell nests of both groups were calculated respectively. It revealed that the amount of PCNA positive cells in the group with little or no MC was significantly more than that in the other group. The ratio between the 2 groups in liver carcinoma was approximately 3:1 and in stomach cancer it was 2:1. An overexpression of EGF gamma was observed in tumor tissues of both groups, but the amount of EGF gamma positive cells in the group with little or no MC was much higher than that of the group with abundant MC.
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PMID:[The expression of PCNA and EGF gamma in tumor cells of experimental hepatocellular carcinoma of liver and squamous cell carcinoma of stomach in rats]. 787 58

Plasma membrane purified from Buffalo rat liver tissue not only had the ability to bind 125I-EGF (2.77 pg of EGF/mg of membrane protein), but also exhibited both high (Kd = 0.08 nM) and low (Kd = 5.67 nM) affinity receptors. However, the binding of EGF to hepatoma plasma membrane was insignificant. EGF receptor in plasma membrane from normal liver tissue was identified by ECL Western blotting using monoclonal anti-EGF receptor antibody and phosphorylated via the stimulation of EGF. This phosphorylation was inhibited by genistein, a tyrosine kinase inhibitor. However, these effects were not observed in hepatoma cell membrane. These results suggest that plasma membrane purified from normal rat liver tissue has a high level of functional EGF receptor, whereas, hepatoma plasma membrane lacks the receptor.
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PMID:Studies of epidermal growth factor (EGF) receptor in plasma membrane from rat liver and hepatoma tissues. 795 Oct 42

We classified hepatic lesions spontaneously developed by Long-Evans with a cinnamon-like coat color (LEC) rats into the following four stages: Normal liver, acute hepatitis, chronic hepatitis, and hepatoma, by biochemical tests of the sera, and anatomical and histopathological examination of the livers. Hepatocyte growth factor (HGF) activity in the sera of LEC rats which developed acute hepatitis, chronic hepatitis, and hepatoma was higher than that of normal LEC rats. In particular, HGF activity in the sera of the LEC rats with acute hepatitis was about 70-fold that of normal LEC rats. However, primary cultured hepatocytes of LEC rats with hepatic lesions were hardly proliferated by stimulation with EGF and insulin in vitro or with increased HGF in vivo. These results suggest that the hepatocytes of LEC rats with hepatic lesions disorder the signal transduction of growth factors.
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PMID:Serum hepatocyte growth factor activity and hepatocyte proliferation in Long-Evans with a cinnamon-like coat color rats with hepatic lesions. 806 53

The glycoprotein tissue-type plasminogen activator (t-PA) is subject to hepatic clearance in humans. Here, the interaction of t-PA with a well-differentiated hepatoma cell line (HepG2) was examined. Suspended HepG2 cells bound 125I-t-PA in a specific, saturable, and reversible fashion through a Ca(2+)-dependent, active site-independent mechanism. Binding isotherms indicated a high affinity system with a single class of saturable binding sites (Kd 39 nM; maximum binding capacity 493,000 sites per cell). Bound t-PA was rapidly degraded at 37 degrees C in a manner inhibited by lysosomotropic agents or metabolic inhibitors. Pretreatment of t-PA with monoclonal antibodies against the EGF/fibronectin finger domain, but not kringle 2 or kringle 1, reduced total binding by 86%. Binding of 125I-t-PA to HepG2 cells was inhibited by monosaccharides fucose and galactose and by the neoglycoprotein fucosyl-albumin. Enzymatic removal of alpha-fucose residues, but not alpha-galactose, high mannose, or complex oligosaccharide from 125I-t-PA, reduced specific binding by 60 +/- 5%. Binding was also inhibited by high, but not low, molecular weight urokinase, which contains an EGF-based threonine-linked alpha-fucose homologous to that of t-PA. These data suggest that EGF-associated O-linked alpha-fucose may mediate t-PA binding and degradation by HepG2 cells. This mechanism may be relevant to other proteins with analogous structures.
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PMID:alpha-Fucose-mediated binding and degradation of tissue-type plasminogen activator by HepG2 cells. 811 82

We have previously demonstrated that O-phospho-L-tyrosine (P-Tyr), a substrate for a wide range of PTPases, inhibits the growth of human renal cell carcinoma and human breast cancer cell lines and suppresses EGF-mediated EGFR tyrosine phosphorylation. We now show that P-Tyr inhibited the growth of the human hepatoma cell line HEPG2, and src transformed NIH3T3 cells, but did not inhibit the growth of human ovarian carcinoma SKOV-3 cells. Addition of exogenous P-Tyr inhibited the insulin triggered insulin receptor (IR) tyrosine phosphorylation in the HEPG2 cell line and the tyrosine phosphorylation of a variety of cellular proteins in src-transformed NIH3T3 cells. P-Tyr did not inhibit the tyrosine phosphorylation of gp185 erbB-2 in P-Tyr resistant SKOV-3 cells. Thus, inhibition of cell growth by P-tyr was associated with decreased tyrosine phosphorylation of cellular proteins.
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PMID:Association of inhibition of cell growth by O-phospho-L-tyrosine with decreased tyrosine phosphorylation. 860 80


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