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)

Whether the gene expression of hepatic Ca(2+)-binding protein regucalcin is altered in hepatomas was investigated. The change in regucalcin mRNA levels was analyzed by Northern blotting using liver regucalcin complementary DNA (0.9 kb). Rat hepatoma was induced by continuous feeding of basal diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). After 35 weeks feeding, rats were sacrificed, and the non-tumorous and tumorous tissues of the livers were removed. In individual rats, the regucalcin mRNA levels in the tumorous tissues were generally decreased in comparison with that of the non-tumorous tissues of the chemical-fed rats, although the chemical administration might decrease the mRNA expression in normal rat liver, suggesting that the chemical administration causes a suppressive effect on the mRNA expression. When the genomic DNA extracted from the liver tumorous tissues was digested with restriction enzymes (EcoRI, BamHI and HindIII) and analyzed by Southern blotting, no rear-ranged band was found in the regucalcin gene from the hepatoma. Interestingly, in the transplantable Morris hepatoma cells, the regucalcin mRNA was markedly expressed, while the albumin mRNA was expressed only slightly. The present study demonstrates that regucalcin mRNA is clearly expressed in the transformed cells (Morris hepatoma cells).
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PMID:Expression of calcium-binding protein regucalcin mRNA in hepatoma cells. 871 43

The expression of hepatic Ca(2+)-binding protein regucalcin in the cloned human hepatoma cells (HepG2) was investigated. The change in regucalcin mRNA levels was analyzed by Northern blotting using rat liver regucalcin complementary DNA (0.9 kb of open reading frame). Regucalcin mRNA was expressed in HepG2 cells, although the mRNA was markedly expressed in normal rat liver. Moreover, regucalcin protein in HepG2 cells was detected by Western blot analysis using a polyclonal rabbit anti-regucalcin antibody. Regucalcin mRNA expression in HepG2 cells was clearly stimulated by the culture with insulin (10(-8) M) of the effective concentration. Regucalcin protein in HepG2 cells was also increased by the treatment of insulin (10(-8) M). The present results demonstrate that regucalcin is expressed in the transformed HepG2 cells, and that the expression is stimulated by insulin.
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PMID:Expression of calcium-binding protein regucalcin mRNA in the cloned human hepatoma cells (HepG2): stimulation by insulin. 935 48

mRNA of the Ca2+-binding protein, regucalcin, is mainly expressed in the liver and only to a small extent in the kidney, and the expression of hepatic regucalcin mRNA is markedly stimulated by Ca2+ administration [Shimokawa and Yamaguchi (1992) FEBS Lett. 305, 151-154]. The existence of nuclear factors that bind to the 5'-flanking region of the rat regucalcin gene was investigated. When nuclear proteins obtained from various rat tissues were used in gel mobility-shift assays, tissue-specific formation of a protein-DNA complex was found in the liver and kidney. An additional novel protein-DNA complex was formed when liver nuclear extracts obtained from Ca2+-administered rats (10mg of Ca2+/100g body weight) were used. Competition gel mobility-shift experiments using consensus and mutant oligonucleotides for AP-1 factor showed that the additional novel complex was formed from binding of the AP-1 factor to the regucalcin gene. Ca2+-induced binding of the AP-1 factor to the regucalcin gene was completely inhibited by simultaneous administration of trifluoperazine, an antagonist of calmodulin, suggesting that the activation of nuclear AP-1 protein is partly mediated through a Ca2+/calmodulin-dependent pathway. Moreover, the 5'-flanking region of the rat regucalcin gene ligated to a luciferase reporter gene possessed the promoter activity in H4-II-E hepatoma cells. This promoter activity was enhanced by treatment with Bay K 8644, a Ca2+-channel agonist. The present study demonstrates that the Ca2+-response sequences are located within the 5'-flanking region of the rat regucalcin gene.
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PMID:Ca2+ administration stimulates the binding of AP-1 factor to the 5'-flanking region of the rat gene for the Ca2+-binding protein regucalcin. 940 89

Regucalcin is a novel calcium-binding protein which does not contain EF-hand motif as a Ca2+-binding domain. The organization of the rat regucalcin gene consists of seven exons and six introns. Its mRNA is mainly present in liver but slightly in kidney with a size of 1.8 kb. Hepatic regucalcin mRNA expression is stimulated by various factors including calcium, calcitonin, insulin, and oestrogen in rats. The mRNA is also expressed in hepatoma cells (Morris hepatoma and HepG2). Regucalcin plays a role in the maintenance of cytosolic Ca2+ homeostasis in liver cells. Moreover, regucalcin has an inhibitory effect on Ca2+/calmodulin-dependent enzyme activation, protein kinase C activation, and many Ca2+-activated enzymes, indicating a role in the regulation of the Ca2+-signalling system. Recently, regucalcin has been demonstrated to regulate nuclear function in liver cells. Regucalcin can inhibit Ca2+-activated nuclear DNA fragmentation in rat isolated liver nuclei. Furthermore, the liver nuclear DNA and RNA syntheses are inhibited by regucalcin. Such an effect of regucalcin is also seen in the nuclei of regenerating rat liver. The regucalcin mRNA level is increased in regenerating liver. These findings suggest that regucalcin plays a regulatory role in the suppression for overexpression of proliferative cells.
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PMID:Role of calcium-binding protein regucalcin in regenerating rat liver. 979 43

To understand the mechanism underlying the regulation of the Ca2+-binding protein regucalcin gene expression, we characterized the 5'-flanking region of the rat regucalcin gene. The transcriptional start site of the rat regucalcin gene was determined by the cap site hunting method with rat liver cap site cDNA. The 5'-flanking region of the rat regucalcin gene ligated to a luciferase reporter gene possessed functional promoter activity in rat H4-II-E hepatoma cells. 3'- and 5'-deletion analyses indicated the sequence required for basal functional promoter activity of the rat regucalcin gene. The promoter activity of the rat regucalcin gene was enhanced by treatment with Bay K 8644, dibutyryl cAMP, phorbol esters, insulin, and dexamethasone. Using gel mobility shift assays, we found that nuclear proteins from H4-II-E cells specifically bind to the 5'-flanking region of the rat regucalcin gene. Moreover, gel mobility shift assays revealed that Bay K 8644, dibutyryl cAMP, phorbol esters, and insulin stimulated the binding of nuclear factors to the 5'-flanking region of the rat regucalcin gene in H4-II-E cells. These results suggest that Bay K 8644-, dibutyryl cAMP-, phorbol ester-, and insulin-inducible nuclear factors mediate the stimulatory effect of each regulator on promoter activity of the rat regucalcin gene.
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PMID:Promoter characterization of the rat gene for Ca2+-binding protein regucalcin. Transcriptional regulation by signaling factors. 988 Apr 96

The involvement of signaling factors, which are related to serum component, on the regucalcin mRNA expression in the cloned rat hepatoma cells (H4-II-E) was investigated. The change in regucalcin mRNA levels was analyzed by Northern blotting using rat liver regucalcin complementary DNA (0.9 kb of open reading frame). H4-II-E cells were cultured for 2 or 6 h in a medium containing various reagents in the presence of serum (10% fetal bovine serum) after the subconfluent with 3-day-culture. The regucalcin mRNA expression was significantly increased by serum addition. This increase was clearly inhibited by the presence of EGTA (10(-3) M), A23187 (10(-6) M), trifluoperazine (10(-5) M), staurosporine (10(-7) M), or genistein (10(-5) M) with 6-h-culture, although the beta-actin mRNA expression was not altered by the reagents. Meanwhile, the regucalcin mRNA expression was significantly stimulated by the addition of Bay K 8644 (2.5 x 10(-6) M) in the presence of serum. This effect was also seen in the presence of genistein (10(-5) M). The present study suggests that the regucalcin mRNA expression is mediated through signaling pathways which are partly involved in Ca2+-dependent protein kinases and tyrosine kinase in H4-II-E hepatoma cells.
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PMID:Involvement of intracellular signaling factors in the serum-enhanced Ca2+-binding protein regucalcin mRNA expression in the cloned rat hepatoma cells (H4-II-E). 1038 Dec 64

The expression of hepatic Ca2+-binding protein regucalcin in the cloned rat hepatoma cells (H4-II-E) was investigated. The change in regucalcin mRNA levels was analyzed by Northern blotting using rat liver regucalcin complementary DNA (0.9 kb of open reading frame). Regucalcin mRNA was expressed in H4-II-E hepatoma cells. This expression was clearly stimulated in the presence of serum (10% fetal bovine serum). Bay K 8644 (2. 5 x 10(-6) M), a Ca2+ channel agonist, significantly stimulated regucalcin mRNA expression in the absence or presence of 10% serum. Dibutyryl cyclic AMP (10(-3) M) did not have a stimulatory effect on the regucalcin mRNA expression. The presence of phorbol 12-myristate 13-acetate (PMA; 10(-6) M) or estrogen (10(-8) M) caused a significant increase in regucalcin mRNA levels in the hepatoma cells cultured in serum-free medium, while insulin (5 x 10(-9) M) or dexamethasone (10(-6) M) had no effect. Bay K 8644-stimulated regucalcin mRNA expression in the hepatoma cells was completely blocked in the presence of trifluoperazine (10(-5) M), an antagonist of calmodulin, or staurosporine (10(-7) M), an inhibitor of protein kinase C. The stimulatory effect of PMA was clearly inhibited in the presence of stauroporine. The present study demonstrates that regucalcin mRNA is expressed in the transformed H4-II-E hepatoma cells, and that the expression is stimulated through Ca2+-dependent signaling factors.
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PMID:Expression of calcium-binding protein regucalcin mRNA in the cloned rat hepatoma cells (H4-II-E) is stimulated through Ca2+ signaling factors: involvement of protein kinase C. 1049 83

Regucalcin is a Ca2+-binding protein which plays a regulatory role in liver cell functions related to Ca2+. In this study we have cloned and characterized cDNA for regucalcin from human liver and human hepatoma cell line Hep G2 by screening and rapid amplification of cDNA ends (RACE). The nucleotide sequences of the clones revealed that they were identical in their coding region and differed only in their 5' untranslated regions (UTRs). Northern blot analysis showed that regucalcin mRNA in the Hep G2 was longer than that of the liver. The present study demonstrates the existence of transcript heterogeneity of the human gene for regucalcin.
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PMID:Transcript heterogeneity of the human gene for Ca2+-binding protein regucalcin. 1067 70

The characterization of the binding of nuclear protein on the 5'-flanking region of the rat regucalcin gene was investigated. Nuclear extracts from rat liver and H4-II-E hepatoma cells were used for oligonucleotide competition gel mobility shift assay. An oligonucleotide between position -523 and -506 in the 5'-flanking region of the rat regucalcin gene, which contains a nuclear factor I (NF1) consensus motif TTGGC(N)(6)CC, competed with the probe for the binding of the nuclear proteins from rat liver and H4-II-E cells. The mutation of TTGGC in the consensus sequence caused an inhibition of the binding of nuclear factors. The presence of Bay K 8644, insulin, and phorbol esters could stimulate the binding of the nuclear factors to the TTGGC region of the rat regucalcin gene in H4-II-E cells. The specific mutation introduced in this region, which was ligated to a luciferase reporter gene, reduced significantly the effects of Bay K 8644, insulin, and phorbol esters in stimulating the regucalcin gene transcriptional activity in H4-II-E cells. These results suggest that the specific nuclear factor binds to the NF1-like sequence, which can stimulate the transcriptional activity, in the promoter region of regucalcin gene in liver cells.
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PMID:Involvement of hepatic nuclear factor I binding motif in transcriptional regulation of Ca(2+)-binding protein regucalcin gene. 1069 12

Regucalcin was discovered in 1978 as a calcium-binding protein that does not contain EF-hand motif of Ca(2+)-binding domain [M. Yamaguchi and T. Yamamoto, Chem. Pharm. Bull. 26 1915-1918 (1978)]. In recent years, regucalcin has been demonstrated to play an important role as a regulatory protein in Ca2+ signaling in rat liver and kidney cells. The organization of the rat regucalcin gene consists of seven exons and six introns. The mRNA is mainly present in liver and kidney with a size of 1.8 kb. Hepatic regucalcin mRNA expression has been shown to be stimulated by various factors including calcium, calcitonin, insulin, and estrogen in rats. The mRNA is also expressed in hepatoma cells (Morris hepatoma, HepG2, and rat hepatoma H4-II-E cells). Regucalcin plays a role in the maintenance of intracellular Ca2+ homeostasis due to activating Ca2+ pump enzymes in the plasma membrane (basolateral membrane) and microsomes of liver and renal cortex cells. Moreover, regucalcin has an inhibitory effect on the activation of Ca2+/calmodulin-dependent enzymes and protein kinase C. Also, regucalcin has been demonstrated to regulate nuclear function in liver cells; it can inhibit Ca(2+)-activated DNA fragmentation, DNA and RNA synthesis, protein kinase and protein phosphatase activities in the nuclei. Such an effect is also seen in the nuclei of regenerating rat liver. Regucalcin may play a physiological role in the control for overexpression of proliferative cells. Regucalcin has been proposed to be an important regulatory protein in Ca2+ signaling system, and it plays a multifunctional role in liver and kidney cells.
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PMID:Role of regucalcin in calcium signaling. 1080 75


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