Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four isoenzymes of hexokinase were isolated by means of chromatography on DEAE-cellulose from soluble fraction of Vistar rat liver tissue. One of the isoenzymes (IV) was a glucokinase. Four fractions were also found in starch gel electrophoresis. These fractions catalyzed phosphorylation of glucose. Besides alterations in the total activity of hexokinase the changes in isoenzyme spectra were observed in carcinogenesis, caused by diethyl nitrosoamine. In the course of development of the blastomatose process in liver tissue content of isoenzymes I, II and, especially, of III was increased, and content of isoenzyme IV was decreased. In tissue of primary hepatomas, induced by diethyl nitrosoamine, the isoenzyme spectra of hexokinase did not significantly differ from the spectra of the enzyme in liver tissue at later stages of carcinogenesis.
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PMID:[Liver hexokinase isoenzymes in carcinogenesis]. 16 15

Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetylaminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demonstrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.
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PMID:Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver. 304 Jul 65

Hepatocyte-like mhAT3F cells have been derived from the hepatoma of a transgenic mouse expressing the SV40 large T antigen under the control of the antithrombin III gene regulatory region (Antoine, B., Levrat, F., Vallet, V., Berbar, T., Cartier, N., Dubois, N., Briand, P., and Kahn, A. (1992) Gene expression in hepatocyte-like lines established by targeted carcinogenesis in transgenic mice. Exp. Cell. Res. 200, 175-185; F. Levrat et al., unpublished results). In these cells, the L-PK gene is transcriptionally activated by glucose, as it is in vivo and in cultured hepatocytes. However, in contrast to the L-PK gene regulation in the liver and isolated hepatocytes, the glucose responsiveness does not require insulin and is not blocked by cyclic AMP. In mhAT3F cells, the insensitivity to insulin might be due to the replacement of insulin-dependent glucokinase by insulin-independent hexokinases able to phosphorylate glucose in the absence of the hormone. The glucose-dependent activation of the L-PK gene is delayed, requires ongoing protein synthesis, and is mediated by the same glucose response element as in vivo and in isolated hepatocytes. These results suggest that the glucose-dependent signaling pathway responsible for the transcriptional activation of glycolytic and lipogenic genes requires glucose phosphorylation, a phenomenon that is insulin-dependent in the liver but insulin-independent in cultured hepatoma cells. Nevertheless, the action of glucose 6-phosphate is most likely indirect.
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PMID:Glucose-dependent regulation of the L-pyruvate kinase gene in a hepatoma cell line is independent of insulin and cyclic AMP. 829 94

The appearance of hepatocellular adenomas and carcinomas induced in rat liver with N-nitrosomorpholine is preceded by different types of preneoplastic foci consisting of phenotypically altered hepatocytes. The altered cells show changes in the activities of various enzymes including those of carbohydrate metabolism. Glucokinase is a type of hexokinase that is specific for hepatocytes. The enzyme plays a key role in glucose homeostasis in normal liver parenchyma and is replaced in the dedifferentiated hepatocytes of carcinomas by a low Km hexokinase. To determine the time course of the shift from glucokinase to this isoenzyme in the development of carcinomas, focal hepatic lesions were dissected from freeze-dried serial tissue sections by the laser-dissection method and studied by microbiochemical tests. In early clear and acidophilic cell foci that excessively stored glycogen (glycogenotic foci) a nearly normal glucokinase activity comparable with that of the surrounding hepatocytes was observed, whereas in the later appearing mixed cell foci a reduction in the activity of this enzyme without a compensatory increase in the hexokinase activity was found. A pronounced activity of hexokinase was only measurable in fully developed carcinomas. Since glucokinase is not modified at the post-transcriptional level, a gradual decrease in its mRNA during hepatocarcinogenesis can be assumed. A shift in gene expression from glucokinase to the isoenzyme hexokinase occurs only at the mixed cell foci/carcinoma transition step of the carcinogenic process.
Carcinogenesis 1993 Sep
PMID:Isoenzyme shift from glucokinase to hexokinase is not an early but a late event in hepatocarcinogenesis. 840 10

In an attempt to seek out new factors that are related to colorectal carcinogenesis at the molecular level, subtractive hybridization between cDNA of normal mucosal tissues and mRNA of colorectal carcinoma tissues was performed. Subsequent screenings of the cDNA libraries, constructed from normal mucosal tissues, using the "subtractive probes" generated a total of 46 clones that were expressed in normal mucosa but were either expressed at a significantly reduced level or not expressed at all in cancer tissues. Partial nucleotide sequences of all of these cDNA clones were determined, and sequence homology analyses were performed with the Genbank database. Of the 46 cDNA samples, 44 contained substantial sequence homologies with 32 immunoglobulin gene fragments, a helix-loop-helix basic phosphoprotein gene, an acidic ribosomal phosphoprotein P2 gene, a BLR1 gene for Burkitt's lymphoma receptor 1 gene, D5S419 DNA segment containing (C-A) repeats, a glucokinase (GCK) gene, a Na+, K+-ATPase alpha-subunit gene, a histocompatibility system HLA-DR heavy-chain gene, a dystrophic gene, a mucin (MUC2) gene, a mu-glutathione S-transferase gene, a Menkes disease protein gene, and a 40-kDa keratin intermediate filament precursor gene. The remaining two cDNA clones (now registered under GenBank accession numbers U17714 and U20428) showed few (less than 60%) sequence homologies with any known sequences in the GenBank database and, therefore, may represent novel genes whose expression was down-regulated in human colorectal carcinomas. The possible clinical significance of these findings and the involvement of these two genes in the carcinogenesis of colorectal as well as other cancers are being investigated.
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PMID:Characterization of colorectal-cancer-related cDNA clones obtained by subtractive hybridization screening. 929 8