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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to characterize the genes overexpressed in an hepatoma cell line, the HTC cells, and in diethylnitrosamine induced solid hepatomas, we constructed a complementary DNA library from HTC cells and performed differential screening with probes from HTC cells, from malignant nodules obtained 70 weeks after the carcinogen treatment, and from hepatocytes from normal rat liver. Eight clones corresponding to messenger RNAs (mRNAs) much more expressed in hepatomas than in hepatocytes from normal liver were isolated. Three, clones pHT 71, pHT 13, and pHT 26, were further analyzed by the study of their corresponding transcripts in hepatocytes from regenerating liver and in the hepatocytes from the nontumorous parts of the liver. Clone pHT 71 corresponds to a single 2.3-kilobase mRNA which is present in high levels in carcinoma nodules in hepatoma cell lines, in the nontumorous parts of the liver, and in hepatocytes isolated from regenerating liver 30 h after partial hepatectomy. Clone pHT 13 hybridizes with three distinct transcripts 3.8, 2.6, and 1.6 kilobases long. High levels of the 3.8- and 1.6-kilobase mRNAs are present in carcinoma nodules, in hepatoma cell lines, and in the nontumorous parts of the liver. However, the levels of these RNAs are similar in hepatocytes from regenerating liver and in hepatocytes obtained from normal rat liver. Clone pHT 26 corresponds to a 0.6-kilobase mRNA which exists at a high level only in cancer nodules and in hepatoma cell lines. We were unable to observe any cross-hybridization between these clones and the oncogenes which have been found to be expressed in hepatomas (c-fos, c-Ha-ras, c-Ki-ras, N-ras, and c-myc). The mRNAs corresponding to the three clones have not been detected in various tissues from normal adult rats. Our study shows that a high level of these mRNAs might be associated with rat liver carcinogenesis.
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PMID:Isolation and characterization of complementary DNA clones for genes overexpressed in chemically induced rat hepatomas. 242 72

The expression of the oncogenes c-myc and c-fos was studied in Wistar rats treated according to the resistant hepatocyte model. During early phases of promotion, i.e. the first 4 days after partial hepatectomy (PH) when the growth hormone (GH)-dependent sex difference in outgrowth of preneoplastic foci becomes manifest, c-myc and c-fos expression were compared in livers from males, females and GH-treated males. The expression of c-fos was almost doubled in males when compared to females 1 day after PH, a difference that gradually declined during the following days. In males receiving growth hormone in osmotic minipumps from 1 week after initiation the expression was at about the same level as that in females, c-myc expression was enhanced in males from the first day after PH and remained elevated, with a maximal 2.5-fold increase at day 2, while the expression in females and GH-treated males was practically unchanged. The increased c-myc expression in males and the effect of GH was still apparent 28 days after PH. Nuclear transcription assay showed a 2- to 3-fold higher transcription of the c-myc gene in untreated when compared with GH-treated males at the third day after PH. In conclusion, continuous GH infusion was shown to modulate the expression of c-myc and c-fos during the phase when sex-differentiated promotion is first observed. These findings might reflect a connection between the regulation of these genes and promotion of liver carcinogenesis. They might also be of possible importance for the understanding of the mechanism of hormone-related cancer.
Carcinogenesis 1989 Dec
PMID:Effects of growth hormone on the expression of c-myc and c-fos during early stages of sex-differentiated rat liver carcinogenesis in the resistant hepatocyte model. 248 Jan 91

The level of expression of several cellular protooncogenes is examined at different stages of 7,12-dimethylbenzanthracene (DMBA)-induced tumor development in hamster buccal pouch epithelium (HBPE). Results presented demonstrate overexpression of c-Ha-ras gene at a very early stage of tumor development, and this elevated level of expression of the gene persists throughout the tumorigenesis process. The expression of the cellular protooncogene c-erbB, on the other hand, can be detected only after 8-10 weeks of DMBA treatment of the tissue and increases with the progression of the disease. The overexpression of c-erbB gene can be correlated with the stage of extensive proliferation and subsequent invasion of the HBPE cells into the underlying connective tissue. This sequential pattern of stage-specific expression of the two cellular protooncogenes can be observed in (i) treated tissues, (ii) stage-representative cultured cells, and (iii) NIH 3T3 transformants derived with DNA from HBPE cells. The low-level expression of c-myc and c-sis genes detected in control tissues remains unaffected, while c-fos gene activity cannot be detected at any stage of tumor development. The overexpression of c-Ha-ras gene alone in HBPE cells derived from tissues treated for 5 weeks (DM5) is not sufficient to induce tumors in athymic mice, whereas expression of c-Ha-ras and c-erbB genes at later stages of tumor development (DM10 and HCPC cells) induce histopathologically defined epithelial cell carcinoma in athymic mice within 2-3 weeks. The sequential overexpression of c-Ha-ras and c-erbB genes in a stage-specific manner and their cooperative interaction in the DMBA-induced in vivo oral carcinogenesis have been demonstrated.
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PMID:Sequential expression and cooperative interaction of c-Ha-ras and c-erbB genes in in vivo chemical carcinogenesis. 249 53

The expression of the protooncogenes c-myc, c-fos and c-rasHa has been studied in rats treated according to the resistant hepatocyte model. Protooncogene expression was studied in male and female rat liver during the selection phase, when the outgrowth of putative preneoplastic foci/nodules is markedly faster in males, and compared with the expression in advanced nodules and hepatocellular carcinomas in males. During the first 16 h after partial hepatectomy the expression of c-fos and c-myc showed transient, 2- to 3-fold, increases in both sexes, both in initiated and in 'control' animals, receiving the selection/promotion regiment but no diethylnitrosamine, with a maximum at 0.5 and 2-4 h respectively. c-rasHa exhibited a moderate increase (1.5-fold) at 16-24 h in all groups. A second increase in c-myc expression (2-fold) started 24 h after partial hepatectomy and lasted over the entire selection period in initiated males, while it was unchanged in females and uninitiated males. The c-fos expression also showed a short-lived increase 24 h post partial hepatectomy in initiated males. The expression of c-myc and c-fos was increased 2- to 4-fold in both preneoplastic nodules and hepatocellular carcinomas, whereas c-rasHa expression was unchanged. In conclusion, sex differences were observed in the expression of c-myc and c-fos during the early outgrowth of preneoplastic lesions, possibly reflecting a connection between the expression of these genes and the sex differentiated response to promotion in the resistant hepatocyte model. Furthermore, an overexpression also in later stages of liver carcinogenesis might indicate that expression of the protooncogenes in question is related to the entire process of multistep carcinogenesis in this model.
Carcinogenesis 1989 Oct
PMID:Expression of the c-myc, c-fos and c-rasHa protooncogenes during sex-differentiated rat liver carcinogenesis in the resistant hepatocyte model. 250 86

We have studied whether the Bowman-Birk protease inhibitor (BBI) could affect the expression of c-fos in BALB/c/3T3 cells stimulated to divide with serum. Our results show that the levels of c-fos message are significantly decreased in the presence of antipain and BBI. When the cells were treated with cycloheximide after being grown in the presence of BBI, there was no significant decrease in mRNA levels. Our experiments suggest that a BBI-inhibitable protease may be necessary for c-fos expression in 3T3 cells and that new protein synthesis is required for this hypothesized protease to be active. As BBI is capable of affecting c-fos gene expression in cells without being present in the nucleus, our results suggest that a novel pathway could be involved in c-fos gene expression.
Carcinogenesis 1989 Nov
PMID:c-fos mRNA levels are reduced in the presence of antipain and Bowman-Birk inhibitor. 250 94

It is now evident that development of hepatocellular carcinoma (HCC) in human is associated with a long series of cellular and tissue changes that precede the ultimate development of the cancer. During recent years, enormous progress in molecular research on HCC has been made, particularly in the area of integration of HBV DNA to host cell and oncogene association with carcinogenicity. A high ratio of HCCs from patients in endemic area has integrated HBV DNA in cellular DNA and in some cases, chromosomal translocations associated with HBV integration were observed, suggesting that the integration or the results thereof are connected with cancer development. Employing a DNA-mediated transfection assay using NIH3T3 mouse fibroblasts with high molecular weight DNA, we detected three cellular transforming genes (lca, N-ras, hst) in primary human HCC. However, little is known as to the linkage between the activation of these genes and liver carcinogenesis. In most human primary HCC tissues, at least two oncogenes, c-myc and N-ras are overexpressed, while in some cases other oncogenes c-fos or lca are overexpressed. It is likely that multiple c-oncogens are important in HCC, but specific transcripts for the malignancy of HCC were not detected. At present, we could not find any relationship between the expression of c-oncogenes and integration of HBV, serological markers or the degree of differentiation. Of the experimental animals most frequently used for studies of liver cancer, the rat is best understood and mimics closely many of the lesions in humans. It is of interest to consider that the identification and elucidation of the mechanisms underlying carcinogenic processes in the rat may offer testable hypotheses for steps in the human.
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PMID:[Molecular aspects of human hepatocellular carcinoma]. 253 67

The c-fos gene was used as a probe to detect the Bam HI-digested brain DNA and total RNA isolated from 2 cases of normal human brain and 11 cases of human brain tumor by Southern blot analysis and RNA dot hybridization technique. The result showed an amplification and over-expression of c-fos gene in one case of glioblastoma multiforme. These data suggest that the c-fos gene may take an important role in the carcinogenesis of human primary brain tumor, and the level of c-fos expression may be correlated with the degree of differentiation of brain tumor cells. We also found that there was a rearrangement of c-fos gene in one case of ependymoma. This suggests that, in ependymoma, the c-fos gene may be activated in a way different from that in the brain tumors of astroglia origin.
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PMID:[Amplification, rearrangement and over-expression of c-fos gene in human primary brain tumors]. 256 Apr 57

Our finding that the inhibitors of DNA methylation, 5-azacytidine, 5-azadeoxycytidine or adenosine dialdehyde, given after a carcinogen all potentiated initiation suggested that hypomethylation of DNA during repair synthesis of DNA might play a role in the initiation of the carcinogenic process. To examine this aspect further, we have asked the question, do the nodules which develop from initiated cells after promotion with 1% orotic acid exhibit an altered methylation pattern in their DNA? The methylation status of the DNA from nodules has been examined using the restriction endonucleases HpaII/MspI and HhaI which distinguish between methylated and unmethylated cytosines in their nucleotide recognition DNA 5'-CCGG and 5'-GCGC respectively. The proto-oncogenes, c-myc, c-fos and c-Ha-ras, in the DNA were primarily studied in this investigation because of their possible involvement in cell proliferation and/or in cell transformation and tumorigenesis. The results indicate that in the nodule DNA, c-myc and c-fos are hypomethylated in the sequence of CCGG while the c-Ha-ras shows hypomethylation in the alternating GCGC sequence. This methylation pattern seen in the nodule DNA is not found in the DNA of the non-nodular surrounding liver or liver tissue after exposure to promoter or carcinogen alone. It is also not found in the DNA of regenerating liver. It is particularly significant that the methylation patterns in the c-myc and c-Ha-ras regions are similar to those found in several cancer tissues. The results suggest that this methylation pattern is acquired early in the carcinogenic process and raises the question whether it has any bearing on the process.
Carcinogenesis 1989 May
PMID:Studies on hypomethylation of liver DNA during early stages of chemical carcinogenesis in rat liver. 265 Sep 9

Oxidants can act at multiple stages of carcinogenesis. While they cause genetic damage and are cytotoxic, they also activate cellular pathways which alter gene expression, growth, and differentiation. Certain pathways used by polypeptide growth factors and hormones are also activated by oxidants. For example, oxidants stimulate the phosphorylation of the ribosomal subunit S6, the phosphotransferase activity of protein kinase C, and induce its translocation to the plasma membrane. On the genomic level, oxidants increase the transcription of the growth-competence-related protooncogenes c-fos and c-myc. In addition to these growth factor-type reactions, oxidants induce pathways which are unique to them. Poly ADP-ribosylation of chromosomal proteins is of particular relevance to oxidant carcinogenesis. It represents an epigenetic consequence of DNA-breakage. Both histones and nonhistone proteins are poly ADP-ribosylated in response to oxidants. Among non-histones, ADPR-transferase, topoisomerase I, and the fos oncoprotein were identified as acceptors. Inhibition of poly ADP-ribosylation suppressed the oxidant-induced transcription of c-fos. Since fos oncoprotein serves as a transcriptional regulator, we speculate that its poly ADP-ribosylation and that of other chromosomal proteins plays a role in the modulation of gene expression in response to oxidative stress.
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PMID:Mechanisms of action of oxidant carcinogens. 269 47

A possible role of chromosomal abnormalities in activation of cellular oncogenes is discussed. Data about the types of chromosomal aberrations characteristic of tumours and of expression of oncogenes localized in aberrant chromosomes are compared. For some oncogenes (c-myc, c-myb, c-abl, c-fes, c-fms) a more or less distinct correlation is observed between certain types of chromosomal abnormalities and increase of oncogene expression. On the contrary, one cannot observe such correlation for other group of oncogenes (c-fos, c-ets, c-mos, c-erb-A-1, c-sis, c-src). Chromosomal aberrations are probably one of the mechanisms of cellular oncogene activation during the carcinogenesis.
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PMID:[Chromosome aberrations and cellular antigens]. 332 65


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