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)

We have determined the prevalence of amplification of c-myc, N-myc, L-myc, H-ras, Ki-ras, and N-ras oncogenes in 23 cases of squamous cell carcinoma of the oral cavity, using Southern hybridization analysis of DNA extracted from the primary tumor tissues. Nick-translated oncogene probes and oncogene inserts labeled to high specific activities were used. We observed a 5- to 10-fold amplification of one or more of c-myc, N-myc, Ki-ras and N-ras oncogenes in 56% of the tumor tissue samples, with these oncogenes not being amplified in the peripheral blood cells of the same patients. L-myc and H-ras were not amplified in any of our samples. The oncogene amplifications seemed to be associated with advanced stages of squamous cell carcinomas, with the ras and myc family oncogenes being amplified in stages 3 and 4. Hybridization with N-myc detected an additional 2.3 kb EcoRI fragment, along with the normal 2.1 kb fragment. Our data also demonstrated amplification of multiple oncogenes in the same tumor tissue sample. About 60% of the samples with amplified oncogenes showed simultaneous amplification of 2 or more oncogenes. The results showing different oncogene amplifications in similar tumors, as well as multiple oncogene amplifications in the same tumor, suggest that these oncogenes may be alternatively or simultaneously activated in oral carcinogenesis.
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PMID:Oncogene amplification in squamous cell carcinoma of the oral cavity. 250 19

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

DNAs from mouse skin tumors (papillomas, squamous cell carcinomas, basal cell carcinomas and pilomatrixomas) initiated with X-irradiation and promoted with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) demonstrated dominant transforming activity by the production of transformed foci in the mouse recipient line, NIH3T3. Dominant transforming activity was not found in DNA isolated from normal mouse epidermis or from the corresponding liver. The NIH3T3 transformants induced with squamous cell carcinoma DNA grew in soft agar and formed tumors in nude mice. Southern blot analysis of primary NIH3T3 transformant DNAs carrying oncogenes from radiation-initiated squamous cell carcinomas indicated that the oncogenes responsible for the transformation of the recipient cells were not Ha-ras, Ki-ras or N-ras genes, nor were they erbB, B-lym, met, neu or raf. The data presented indicate that DNAs from radiation-initiated mouse skin tumors contain dominant transforming genes that are detectable by DNA-mediated gene transfer. The oncogene sequences activated in these radiation-initiated tumors are distinct non-ras transforming genes.
Carcinogenesis 1989 Dec
PMID:Detection of distinct transforming genes in X-ray induced tumors. 259 Oct 13

The cell line TE671 has been widely used as a model of human medulloblastoma. In the present study we have demonstrated that transfection of DNA from this cell line into NIH 3T3 cells reveals the presence of an activated N-ras gene. Using oligonucleotide probes we have shown that the N-ras gene is activated by a point mutation at the third base of codon 61 resulting in the substitution of histidine for glutamine in the p21 ras gene product. We noted that this relatively uncommon activating mutation is also present in the human rhabdomyosarcoma cell line RD. Based on this finding and on the observation that several of the phenotypic characteristics of TE671, such as the presence of muscle-type nicotinic acetylcholine receptors and the intermediate filament protein desmin, are suggestive of myoid origin we investigated the possible identity of these two cell lines. Cytogenetic analysis revealed the presence of marker chromosomes common to both TE671 and RD. DNA fingerprinting using both locus specific and multilocus core probes showed indistinguishable band patterns in the two cell lines. Taken together our data show that TE671 and RD are derivatives of the same cell line and we conclude that the properties of the TE671 line should be ascribed to rhabdomyosarcoma rather than medulloblastoma cells.
Carcinogenesis 1989 May
PMID:Characterization of the human cell line TE671. 265 Sep 8

An animal model of carcinogenesis has been exploited to analyze the various events involved in carcinogen-induced T cell lymphomagenesis. Two carcinogenic agents, the alkylating agent N-methylnitrosourea (NMU) and ionizing gamma-radiation, induce tumors in C57BL/6J mice that are phenotypically and histologically identical. Are the genetic events similar or different in the T cell tumors produced by these two carcinogenic agents? NMU treatment produced a different spectrum of activated oncogenes from gamma-irradiation. The K-ras oncogene was preferentially activated in all of the NMU-induced tumors, most frequently by a GGT to GAT transition in codon 12. Ionizing gamma-radiation produced two different transforming activities. Approximately half of the radiation-induced tumors contained activated N-ras genes and half contained a novel non-ras transforming activity. Analysis of NMU- and gamma-irradiated treated animals for chromosomal abnormalities showed anomalies early in the disease. Although both agents produce tumors containing trisomy of chromosome 15, the timing of this event appears to be different occurring early in NMU-induced tumors and later in gamma-radiation induced tumors. In addition, a unique marker chromosome consisting of a translocation between chromosomes one and five appears to be involved in the early stages of radiation-induced disease and may be associated with the novel transforming activity detected in these same tumors. Expression of receptors for the T cell growth factor (IL-2R) is similar in both NMU- and gamma-irradiation induced tumors. Changes in the expression of IL-2R on different T cell populations with disease progression may account for thymus dependent and thymus independent phases of malignant T cell growth.
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PMID:Multistage carcinogenesis in murine thymocytes: involvement of oncogenes, chromosomal imbalances and T cell growth factor receptor. 268 36

To determine if diploid human fibroblasts can be transformed by the N-ras oncogene found in human tumors, early passage cell lines were transfected with an N-ras oncogene from human leukemia cell line 8402 cloned into a high expression plasmid (pSV N-ras), with the N-ras oncogene from human fibrosarcoma cell line HT1080 cloned into pNR-MG1, or with pSV2neo as a control. Each plasmid carries the neo gene coding for Geneticin resistance, but in pSV N-ras, the endogenous promoter of the N-ras gene has been eliminated, and the gene has been inserted between the viral long-terminal repeat (LTR) and the neo gene so that transcription initiated from the LTR must transcribe the N-ras gene before transcribing neo. In pNR-MG1, transcription of the N-ras gene is driven from its endogenous promoter, and the neo gene is transcribed from an SV40 viral promoter, as in pSV2neo. When the transfectants were selected for Geneticin resistance, 70% of the colonies formed with pSV N-ras consisted of morphologically altered cells. Less than 5% of the drug resistant colonies formed with pNR-MG1 had cells with altered morphology, and the change in morphology was much less distinct than with pSV N-ras. No colonies of morphologically-transformed cells were found with pSVneo. If the transfected populations were not selected in Geneticin, but were simply allowed to grow to confluence, very distinct foci composed of morphologically-altered cells could be seen against a contact-inhibited monolayer with pSV N-ras. Foci formed by the pNR-MG1 population were subtle and much less distinct. No foci were found with pSV2neo. Representative colonies and foci of morphologically-transformed cells were isolated. Those from pNR-MG1 transfection reverted to a normal morphology after 5-10 population doublings. Most of those from pSV N-ras transfection either reverted or senesced after 5-10 population doublings. However, progeny of two colonies expressed stable morphological transformation throughout a normal life span equal to that of age-matched pSV2neo controls. Both of these stably transformed cell strains exhibited anchorage independence and formed distinct foci. Immunoprecipitation analysis showed that these cells produced much larger amounts of N-ras protein than did pSV2neo-transfected control cells. However, these two cell strains did not exhibit an infinite life span in culture and were unable to form tumors in athymic mice.
Carcinogenesis 1989 Apr
PMID:Transformation of diploid human fibroblasts by transfection of N-ras-oncogenes. 270 11

The expression of c-Ha-ras-1, Ki-ras, N-ras, abl, src, fos and myc protooncogenes was analyzed in 13 cases of human gastric carcinomas. The transcriptional activity of both fos and myc protooncogenes was found to be disturbed in 47% and 42% of cases, respectively. An overexpression of fos protooncogenes as well as an appearance in some cases of atypical foc-mRNA transcripts were established. Only an elevation of the number of myc mRNA copies was observed. In one patient with gastric carcinoma a c-Ha-ras-1 overexpression was detected due to its amplification both in tumour tissues and in regional metastasis. The expression of other protooncogenes under investigation was similar to those found in normal gastric mucose. In addition, no differences in expression in protooncogenes mentioned above plus sis protooncogene were established in unchanged, premalignant and malignant stomach tissues in the course of N-methyl-N'-nitro-N-nitrosoguanidin-induced carcinogenesis.
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PMID:[Proto-oncogene expression in human carcinomas of the stomach and in the gastric mucosa of rats exposed to N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis]. 292 5

Despite impressive advances in the clinical management of Hodgkin's disease, little is known about its cellular origin or the mechanism(s) of "Hodgkinogenesis." Recent findings that certain human cellular oncogenes can cause malignant transformation suggest that aberrant activation of these genes may play a role in carcinogenesis. To determine if such genes are operative in Hodgkin's cells, we isolated DNA from splenic nodules of three patients with nodular sclerosis Hodgkin's disease and tested its ability to transform mouse NIH 3T3 cells, the standard assay for oncogene-mediated malignant transformation. Transformed cells containing human DNA were obtained from two patients. DNA from these primary transformants yielded secondary transformants of NIH 3T3 fibroblasts; one also transformed normal mouse bone marrow macrophages, a cell type probably related to the Hodgkin's cell. When analyzed by Southern blot methods for homology with closed oncogene probes, the transforming genes from both patients had homology with N-ras. The homology and size of the restriction fragments were similar to those of transforming genes isolated from patients with acute nonlymphocytic leukemias. The presence of the same activated oncogene in tumor tissue from two different patients suggests that it may play an important role in Hodgkinogenesis.
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PMID:Isolation of activated ras transforming genes from two patients with Hodgkin's disease. 298 91

In hepatitis B virus (HBV) related hepatoma samples there is a high frequency of HBV-DNA integration into the chromosome, but the frequency of integration in the early-stage of carcinogenesis is expected to be even higher. Structural an analysis of integrated HBV-DNA and chromosomal flanking DNAs disclosed that the marked rearrangement of chromosomal DNA is not directly linked to carcinogenesis. HBV-DNA integration and chromosomal DNA depletion occur even in chronic hepatitis tissues. Integration is, therefore, thought to trigger a series of reactions which lead to carcinogenesis. However, the oncogene is not detected within the HBV genome, and the HBV integration site in the chromosome is variable. As one approach to clarifying the cause and effect relationship between HBV-DNA integration and liver carcinogenesis DNA transfection experiments were conducted using mouse NIH3T3 cells to detect hepatoma-related oncogenes. As a result, the well-known N-ras gene and an unknown oncogene were independently isolated from different hepatoma tissues.
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PMID:[Hepatitis B virus integration and oncogene activation]. 303 33

Liver cancer is one of the most prevalent forms of cancer in the world. Hepatitis B virus (HBV) is considered to be a major aetiological factor. Evidence from epidemiological studies has also indicated that environmental contaminants such as mycotoxins may, either in combination with HBV or independently, be important aetiological factors in the pathogenesis of primary hepatocellular carcinoma (PHC). Laboratory data also suggest an interplay between viral and chemical factors in the multifactorial aetiology of PHC. Aflatoxin B1, the chemical carcinogen most frequently implicated in the aetiology of hepatocellular carcinoma is a procarcinogen that must be activated by mixed-function oxidases to an electrophilic metabolite before it can exert its carcinogenic effects. Interindividual differences (greater than 10-fold) in the metabolic activation of aflatoxin B1 are observed. These differences may play a part in an individual's oncogenic susceptibility to aflatoxin B1. Chemical carcinogens and integrated HBV may activate cellular oncogenes, eg N-ras, and inactivate tumour suppressor genes. Recently developed methods that allow monitoring of aflatoxin B1 and HBV exposures and also genetic damage caused by these agents in individuals should help in biochemical and molecular epidemiological studies concerning the aetiology of hepatocellular carcinoma. We identify areas of uncertainties and of future experimentation and propose a hypothesis of liver carcinogenesis.
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PMID:Interactive effects of chemical carcinogens and hepatitis B virus in the pathogenesis of hepatocellular carcinoma. 304 Feb 43


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