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)

A monoclonal antibody (mAb 33.4) is described which inhibits the adhesion and spreading of an adherent cell line (A-cells), established from Morris hepatoma 7777 and isolated hepatocytes on collagen IV but not on laminin, fibronectin, and vitronectin. mAb 33.4 retains its immunological activity after immobilization and covalent cross-linking to Protein G-Sepharose and is therefore a suitable tool for the preparative equimolar purification of two proteins with M(r) of 130 and 190 kDa from detergent-solubilized membrane fractions by immunoaffinity chromatography. The 190-kDa protein was identified as rat alpha 1-integrin subunit by N-terminal amino acid sequencing, while the 130-kDa protein was specifically stained by a beta 1-integrin subunit-specific antiserum. In immunoblot analysis mAb 33.4 recognized the 190-kDa band, suggesting that it is specific for the rat alpha 1-integrin subunit. The epitope recognized by mAb 33.4 is conformation-dependent because the staining in immunoblots was very strong if the SDS-PAGE was performed in the absence of reducing agents. The expression of alpha 1 beta 1-integrin in sinusoidal hepatocyte membrane domains of liver sections is shown by mAb 33.4 and antisera raised against the rat alpha 1- and beta 1-integrin subunits.
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PMID:Cell-collagen adhesion is inhibited by monoclonal antibody 33.4 against the rat alpha 1-integrin subunit. 751 46

Fibronectin (FN) is a widely distributed extracellular matrix protein that is essential for cell adhesion in a variety of biological processes such as wound healing, tissue development and remodeling and oncogenic transformation. Appropriate FN levels are obtained by induction or repression of the FN gene in response to specific factors or circumstances in vivo. In order to identify regulatory regions involved in tissue-specific expression of FN, we have examined the transcriptional activity of overlapping fragments, within 4 kb upstream of the rat FN gene, following transfection into different cell types. Two regions conferred increases in transcription. The region between -1.08 and -2.6 displayed tissue-specificity and was active in fibroblasts but not hepatoma cells. The second region, between -3.2 and -3.9, was active in both cell types. Further characterization of the -1.08 to -2.6 segment demonstrated that it acts as an enhancer. Exonuclease III deletions of the 3' and 5' ends of the enhancer localized essential sequences between -1.5 and -1.7 and indicate that this fragment acts in concert with other sites between -1.08 and -2.6 to provide maximum enhancer activity. Gel mobility shift assays demonstrated fibroblast-specific binding of nuclear protein(s) to a 65 bp fragment within the essential region and DNase I footprinting localized this binding to a 27 bp sequence. Deletion of the sequence abolished the activity of the 1.5 kb enhancer. These studies show that a novel DNA sequence at -1688 is involved in regulating transcription of the FN gene in fibroblasts.
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PMID:Identification of an enhancer involved in tissue-specific regulation of the rat fibronectin gene. 766 11

We have previously described a variant form of the integrin beta 1 subunit (beta 1B)1 characterized by an altered sequence at the cytoplasmic domain. Using polyclonal antibodies to a synthetic peptide corresponding to the unique sequence of the beta 1B, we analyzed the expression of this molecule in human tissues and cultured cells. Western blot analysis showed that the beta 1B is expressed in skin and liver and, in lower amounts, in skeletal and cardiac muscles. The protein was not detectable in brain, kidney, and smooth muscle. In vitro cultured keratinocytes and hepatoma cells are positive, but fibroblasts, endothelial cells, and smooth muscle cells are negative. An astrocytoma cell line derived from immortalized fetal astrocytes was found to express beta 1B. In these cells beta 1B represent integral of 30% of the beta 1 and form heterodimers with alpha 1 and alpha 5 subunits. To investigate the functional properties of beta 1B, the full-length cDNA coding for this molecule was transfected into CHO cells. Stable transfectants were selected and the beta 1B was identified by a mAb that discriminate between the transfected human protein and the endogenous hamster beta 1A. Immunoprecipitation experiments indicated that the beta 1B was exported at the cell surface in association with the endogenous hamster alpha subunits. The alpha 5/beta 1B complex bound to a fibronectin-affinity matrix and was specifically released by RGD-containing peptides. Thus beta 1B and beta 1A are similar as far as the alpha/beta association and fibronectin binding are concerned. The two proteins differ, however, in their subcellular localization. Immunofluorescence studies indicated, in fact, that beta 1B, in contrast to beta 1A, does not localize in focal adhesions. The restricted tissue distribution and the distinct subcellular localization, suggest that beta 1B has unique functional properties.
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PMID:Expression and functional analysis of a cytoplasmic domain variant of the beta 1 integrin subunit. 768 33

Tenascin is a novel six-armed extracellular-matrix glycoprotein expressed in association with mesenchymal-epithelial interactions, and its expression is temporally and spatially restricted during organogenesis and carcinogenesis. The distribution and alterations in the expression of fibronectin, laminin, and especially of tenascin, were compared between in vitro and in vivo studies with rat epithelial (hepatocyte-derived) and nonepithelial (sarcoma-derived) cell lines. Immunoprecipitation studies revealed that the production of extracellular-matrix glycoproteins varied among the cell lines. Two ascites-hepatoma-derived cell lines and one sarcoma-derived line were found to synthesize tenascin in vitro. Their major tenascin isoform yielded a molecular weight of 220 kDa under reducing conditions. The other cell lines examined, including all of those derived from normal hepatocytes, were negative for the expression of tenascin. Coculture studies were performed between epithelial and nonepithelial cell lines. No drastic change in tenascin expression was found after coculturing the cells. As an in vivo study, cell lines were transplanted into nude mice. All xenografts of the epithelial lines were associated with a strong positive reaction for extracellular-matrix glycoproteins, and especially for tenascin, in the mouse fibrous stroma adjacent to them. This represents the epithelial induction of stromal tenascin. Whether or not they produced tenascin in vitro, after transplantation none of the epithelial cell lines themselves produced tenascin, whereas both of the nonepithelial cell lines prominently produced tenascin. These findings suggest that, in the process of interactions between epithelial and nonepithelial cells, the expression of tenascin depends on the switch from in vitro to in vivo.
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PMID:Tenascin expression in vitro and in vivo: comparison between epithelial and nonepithelial rat cell lines. 768 94

We have established and characterized a new glioblastoma cell line, termed GT9, from a biopsy sample of a female adult patient with glioblastoma multiforme. The line has now undergone over 60 passages and has been successfully cultured after cryopreservation. Immunofluorescence analyses with a panel of monoclonal antibodies were positive for glial fibrillary acidic protein and vimentin, and negative for neurofilament, galactocerebroside, and fibronectin, a pattern typical of glial cells. Based on a tetraploid, the composite karyotype of GT9 cells included the loss of chromosome 10, gain of chromosome 7, and the presence of double minute chromosomes, three of the most common karyotypic abnormalities in glioblastoma. Sequence analysis of p53 cDNA revealed a homozygous double mutation at codon 249 (commonly mutated in aflatoxin-associated hepatocellular carcinoma) and codon 250. Moreover, there was a complete absence of wild-type p53. However, unlike the majority of human glioblastomas previously described, the expression of platelet-derived growth factor-B (PDGF-B), a potent mitogenic autocrine factor, was low in GT9 cells. The expression and phosphorylation of c-Jun and Jun-B, downstream mediators of the PDGF pathway, were also low. Thus, deregulation of the PDGF pathway does not appear to be involved in the pathogenesis of the GT9 glioblastoma. Conversely, Jun-D, a negative regulator of cell growth, was also low. In addition, Phosphorylated Egr-1, a recently reported suppressor of PDGF-B/v-sis-transformed cells, was also low, suggesting that the lack of activation of the PDGF pathway was not due to these suppressive mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a new human glioblastoma cell line that expresses mutant p53 and lacks activation of the PDGF pathway. 775 3

A case of cirrhotic liver harbouring three atypical macroregenerative nodules and an hepatocellular carcinoma was immunocytochemically investigated for the expression of VLA-beta 1, VLA-alpha 2 and VLA-alpha 5 integrins and for different extracellular matrix (ECM) components (collagen I, collagen IV, laminin, fibronectin and tenascin). In addition, the proliferative activity within the nodules was evaluated, using the MIB 1 monoclonal antibody (MAb). The cirrhotic liver disclosed a continuous staining pattern of the ECM proteins investigated, as well as a "sinusoidal" immunostaining of VLA-beta 1, VLA-alpha 2 and VLA-alpha 5. The macroregenerative nodules showed a discontinued immunoreactivity for ECM proteins while maintaining a VLA-beta 1 sinusoidal immunostaining, coupled with intercellular immunostaining. VLA-alpha 2 and VLA-alpha 5 expression was lacking. The growth fraction was low in both the above pathological conditions. The hepatocellular carcinoma was devoid of any ECM immunostaining. VLA-beta 1 immunoreactivity exhibited a honeycomb pattern of staining, whereas VLA alpha subunits were absent. MIB1 expression was high, being present in 30% of neoplastic nuclei. A possible relationship between atypical macroregenerative nodules and hepatocellular carcinoma is discussed.
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PMID:Extracellular matrix proteins, integrin receptors (VLA-beta 1, VLA-alpha 2 and VLA-alpha 5) and growth fraction in atypical macroregenerative nodules of the liver: an immunocytochemical case study. 781 67

The amino 3'-glycosyl phosphotransferase (neo) gene is the selectable marker most widely used in stable transfection or infection protocols. Because the neo gene product has phosphotransferase activity, it might modify the phosphorylation state when introduced in mammalian cells. NIH-3T3 fibroblast cells expressing the neo gene, after either infection with retroviral vectors or transfection with plasmids, showed a 50% reduction in both fructose 2,6-bisphosphate (Fru 2,6-P2) concentration and lactate production compared with control NIH-3T3 cells, indicating that these neo-expressing cells are less glycolytic. In addition, a marked decrease in the levels of mRNA for the procollagen 1 alpha and fibronectin genes was also observed in neo-expressing NIH-3T3 cells. This decrease was concomitant with an increase in the mRNA concentration of the endogenous c-myc gene. FTO-2B rat hepatoma cells also showed modifications in gene expression when the neo gene was introduced by stable transfection or infection. In these cells an increase in both P-enolpyruvate carboxykinase (PEPCK) and tyrosine aminotransferase (TAT) mRNA was observed. These results suggest that neo gene expression may induce changes in the cells, which should be considered when neo-selected cells are used to deliver specific genes in different therapy approaches and in embryo manipulation.
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PMID:Expression of the neomycin-resistance (neo) gene induces alterations in gene expression and metabolism. 791 94

In heparinized human platelet-rich plasma (PRP), J-7 human hepatoma cells initially induced platelet aggregation; then a clot formed. ADP-scavenger systems, apyrase and creatine phosphate/creatine phosphokinase did not inhibit this tumor-cell-induced platelet aggregation (TCIPA), whereas hirudin and concanavalin A completely blocked it. J-7 cells also shortened the recalcification time of normal and of Factor-VIII- and IX-deficient human plasma, although it was inactive in shortening the recalcification time of Factor-VII-deficient plasma. After treatment with phorbol 12,13-dibutyrate (PDBu) for 5 to 90 min, the aggregation and coagulation abilities of J-7 cells were unaffected. Prolonged treatment of J-7 cells with PDBu but not with alpha-PDBu for 24 and 72 hr resulted in gradual loss of aggregation and coagulation. Staurosporine antagonized the effect of PDBu and restored aggregation and coagulation in J-7 cells. Protracted treatment with PDBu (24 or 72 hr) did not affect adherence of J-7 cells to the extracellular-matrix proteins (i.e., fibrinogen, fibronectin, laminin, vitronectin and collagen types I and IV) or to the surface of plastic culture dishes. The treatment also did not affect J-7 cell detachment from plastic culture dishes. These in vitro results demonstrate that protracted phorbol ester treatment diminishes TCIPA and blood coagulation of tumor cells.
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PMID:Protracted treatment with phorbol ester modulates J-7 human hepatoma-cell-induced aggregation and coagulation of human platelet-rich plasma. 796 Feb 44

This study investigated cells producing type I, III, and IV collagens, laminin, and fibronectin, the major components of the extracellular matrix, and compared their localization patterns in relation to the grade of tumor differentiation and the histological pattern of hepatocellular carcinoma. Type I, III, and IV collagens, laminin, and fibronectin were produced by tumor, endothelial, and Ito cells. Regarding their localization pattern in relation to the histological pattern of tumors, although the extracellular matrix was present in the subendothelial spaces of sinusoids in every histological pattern, the localization of these components in the intercellular spaces of tumor cells was most marked in hepatocellular carcinoma with a compact pattern. These results suggest that the extracellular matrix produced by tumor, endothelial, and Ito cells is deposited in appropriate positions in hepatocellular carcinoma to sustain the tissue structure showing different histological patterns. In relation to the grade of tumor differentiation, in most cases, Type I, III, and IV collagens and fibronectin were present in the subendothelial spaces of sinusoids and the intercellular spaces of some tumor cells, while little laminin was observed in well-differentiated small hepatocellular carcinoma (less than 10 mm diameter). In undifferentiated hepatocellular carcinoma, little extracellular matrix was observed, except around vessels. These results suggest that sinusoidal capillarization may not yet have occurred in the early stage of hepatocarcinogenesis, although it develops as the tumors increase in size and the tumor cells dedifferentiate. In undifferentiated hepatocellular carcinoma, tumor cells are too atypical to produce each extracellular matrix component.
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PMID:The extracellular matrix in hepatocellular carcinoma shows different localization patterns depending on the differentiation and the histological pattern of tumors: immunohistochemical analysis. 796 19

We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF-1, was established from a hepatocellular carcinoma of a 67-yr-old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI-1640 tissue-culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, alpha 2-macroglobulin, fibronectin and alpha-fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF-1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload.
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PMID:Establishment of a cell line from a hepatocellular carcinoma from a patient with hemochromatosis. 802 Sep 7


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