Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that the human liver-specific antigen (HLSA) expression was enhanced and c-myc levels were reduced during sodium butyrate-induced differentiation in human hepatoma cells. To further elucidate a linkage between the reduction of c-myc levels and an increase in the HLSA expression, antisense oligodeoxynucleotide against c-myc mRNA was transferred into human hepatoma cells. Human hepatoma cell lines, HCC-M, HCC-T and PLC/PRF/5 were transfected with antisense oligodeoxynucleotide and changes in the cell cycle, expression of the HLSA, albumin, and alpha-fetoprotein were examined. Antisense oligodeoxynucleotide was successfully induced into cells visualized by a confocal microscope using fluorescein-labeled oligodeoxynucleotides, and Northern blot analysis revealed that c-myc expression was reduced three and six hours after the transfection. Following these changes, cell proliferation was inhibited and flow cytometric analysis showed that cell number in the G1 phase significantly increased. Increased expression of the HLSA and albumin, and decreased expression of alpha-fetoprotein was observed by flow cytometry in accordance with those changes. These results showed similar changes to those induced by butyrate-treatment obtained in our previous studies. The present study indicates that the reduction of c-myc transcription increases HLSA expression levels through intracellular changes similar to those induced by butyrate, a differentiation inducer.
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PMID:Antisense oligodeoxynucleotide against c-myc mRNA induces differentiation of human hepatocellular carcinoma cells. 1053 84

A ribozyme (RZ) gene targeting c-myc mRNA was synthesized and cloned. Cleavage reaction showed that cleavage of the RZ was efficient and specific. The RZ gene-containing retrovirus vector pDOR-RZ was transfected into HCC-9204 hepatoma cells, which constitutively express high levels of c-myc using Lipofectamine. Positively transfected cells were selected using G418. In situ hybridization showed that both pDOR-RZ and pDOR vectors had been integrated into the chromosome of HCC-9204 cells. Dot blot hybridization indicated that expression of the RZ was only evident in pDOR-RZ-transfected HCC-9204 cells. Avidin-biotin complex enzyme-linked immunosorbent assay showed that c-myc expression was down-regulated. Chromatin aggregation into compact masses, cytoplasmic vacuole degeneration, and blurring of cytoplasm structure were observed by transmission electron microscopy in HCC-9204-RZ cells. These results suggest that the use of a c-myc mRNA cleaving enzyme could be most effective in tumor cells that are highly proliferative and constitutively express high levels of c-myc.
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PMID:Inhibition of cell proliferation in HCC-9204 hepatoma cells by a c-myc specific ribozyme. 1076 46

c-Myc has been documented to be both a positive and a negative signal for the induction of apoptosis. It is well known that overexpression of the c-myc gene induces apoptosis of normal cells, but the result of a reduction in its expression is not fully understood. We examined whether a reduction in c-myc expression would induce apoptosis in human liver cancer cells. Specifically, antisense and sense oligodeoxynucleotides (oligos) against the human c-myc mRNA were synthesized, mixed with a liposome reagent at various ratios, and were applied to the liver cancer-derived cell lines, HCC-T, HepG2, and PLC/PRF/5. To exclude effects resulting from using oligos, plasmid vectors expressing the full-length c-myc cDNA in both sense and antisense orientations under the control of the Cre/loxP system were generated. Monoclonal cell lines including these plasmid vectors were produced and Cre was supplied by adenovirus infection. Apoptosis was determined morphologically and c-Myc and Bcl-2 expression was examined by Western blotting. The antisense myc significantly inhibited the proliferation of the cells within two days, while neither the liposome reagent alone nor sense myc did so. Most of the cells were rounded up by the antisense-treatment and nuclear fragmentation and DNA ladder formation were detected after two days in antisense c-myc-treated cells. Antisense c-myc largely reduced c-Myc and partially Bcl-2 expression; overexpression of Bcl-2 partially rescued from apoptosis in HCC-T and HepG2 cells. These results suggest that the massive reduction in c-myc mRNA induces apoptosis in liver cancer cell lines and consequent decrease in Bcl-2 enhances the cell death. c-Myc reduction under the Cre/loxP switching system may be a useful tool for the clarification of c-myc-related cellular mechanisms in differentiation and proliferation.
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PMID:Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells. 1138 22

Prothymosin-alpha (PTalpha) is known to play a role in cell proliferation, and the PTalpha mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTalpha mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTalpha and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTalpha and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTalpha mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTalpha and c-myc. PTalpha mRNA overexpression in lung cancer was correlated with a poor prognosis.
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PMID:Expression of the prothymosin-a gene as a prognostic factor in lung cancer. 1175 95

There is considerable evidence that reactive oxygen species (ROS) have a causative role in chronic hepatic injury and cancer development via direct and indirect mechanisms. Estrogens produce free oxygen radicals through redox cycling and affect cell proliferation, also in the liver. We are presently involved in evaluating the possible relationship between estrogens receptor expression, type of receptor, oxidative DNA damage and c-myc in chronic liver disease. The data on DNA adducts, c-myc mRNA and variant estrogen receptor in patients with HCV- or HBV-related chronic liver disease are suggesting that those positive for variant liver estrogen receptor present higher genomic oxidative damage, as reflected in 8-OHdG levels. We are also observing that patients with chronic hepatitis and cirrhosis, when positive for variant estrogen receptor, present higher c-myc m-RNA expression, a factor reportedly associated with increased genomic instability, augmented cytoproliferation and carcinogenesis. Our own and other author's data are shedding new light on estrogen pathophysiology, liver damage and hepatic cancer.
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PMID:Estrogens receptors and oxidative damage in the liver. 1216 Oct 6

Peroxisome proliferator chemicals are classic non-genotoxic carcinogens. These agents cause liver cancers when chronically administered to rats and mice. Peroxisome proliferators include the widely prescribed lipid and cholesterol lowering fibrate drugs. In contrast to the results in rodents, there is no evidence that fibrates are associated with elevated risk of liver cancer or any other neoplasms in humans thus indicating a species difference in the hepatocarcinogenic response. The biological effects of peroxisome proliferators are mediated by the peroxisome proliferator-activated receptor (PPAR)alpha. Pparalpha-null mice are resistant to all of the pleiotropic effects of peroxisome proliferators, including cell proliferation and hepatocarcinogenesis. The mechanism of hepatocellular proliferation involves downregulation of the microRNA let-7c gene by PPARalpha. Let-7c controls levels of proliferative c-myc by destabilizing its mRNA. Thus, upon suppression of let-7c, c-myc mRNA and protein are elevated resulting in enhanced hepatocellular proliferation. In contrast, PPARalpha-humanized mice, that respond to Wy-14,643 by lower serum triglycerides and induction of genes encoding fatty acid metabolizing enzymes, are resistant to peroxisome proliferator-induced cell proliferation and cancer. These mice do not exhibit downregulation of let-7c gene expression thus forming the basis for the resistance to hepatocellular carcinogenesis.
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PMID:PPARalpha: mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators. 1800 36

To investigate the regulatory role of microRNA-223 (miR-223) on c-myc and its role in hepatocarcinogenesis. miR-223 and c-myc mRNA expressions in normal tissue, paraneoplastic tissue, liver cancer tissue and liver cancer cells were tested with microRNA microarray and quantitative real-time PCR (qRT-PCR). C-myc protein expression was detected by Western blot. MiR-223 mimic was transfected into HepG2 cells and the expression changes of c-myc mRNA and protein were tested with qRT-PCR and Western blot respectively. MiR-223 was down-regulated by 61.53% and 30.77% respectively in hepatocellular carcinoma and adjacent tissues as compared to normal liver tissues and the expression of miR-223 was also decreased in HepG2 cell as compared to fetal liver cells L02, whereas the expressions of c-myc mRNA and protein increased in paraneoplastic and HCC tissues compared with normal liver tissues. It prompts that the expressions of miR-223 and c-myc are negatively correlated. No obvious difference found among c-myc mRNA expressions after miR-223 mimics transfection. The c-myc abnormal high-expression may play a dynamic role in hepatocarcinogenesis due to the miR-223 down-regulation.
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PMID:[Role of microRNA-223 and its target gene oncogene c-myc in hepatocellular carcinoma pathogenesis]. 2149 14