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)

The DNA sequences around codons 12, 13, and 61 of the ras gene were analyzed by polymerase chain reaction and direct sequencing in 18 intrahepatic cholangiocarcinomas. The ras gene mutations were found in 9 of 18 (50%): 6 in K-ras codon 12, 1 in K-ras codon 13, 1 in K-ras codon 61, and 1 in N-ras codon 12. The incidence of mutations was higher in the hilar type of intrahepatic cholangiocarcinomas, especially when these tumors were large. The incidence and spectrum of the mutations were almost the same as those reported in colon cancers, possibly indicating similar etiologic agent(s) in the carcinogenesis of both cancers.
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PMID:High incidence of ras gene mutation in intrahepatic cholangiocarcinoma. 173 10

Pulmonary carcinogenesis due to occupational and environmental exposures to chemical carcinogens such as polycyclic aromatic hydrocarbons presents an interesting model for study of possible oncogene-related cancer biomarkers. Polycyclic aromatic hydrocarbons are important respiratory carcinogens and have been shown to cause specific mutational lesions that can lead to the activation of the ras oncogene and expression of its p21 protein product; ras oncogene activation and p21 expression frequently are detected in human lung cancers. In addition, the p21 protein is detectable via immunoblotting techniques in the serum of lung cancer patients and in selected persons in exposed worker cohorts at risk for the development of lung cancer. Thus, the ras oncogene and p21 protein may be useful biomarkers for monitoring pulmonary carcinogenesis in exposed populations.
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PMID:Advances in cancer biomarkers as applied to chemical exposures: the ras oncogene and p21 protein and pulmonary carcinogenesis. 174 43

Evaluation of molecular events in human colon polyps and tumors has revealed constitutive elevated expression of c-myc, activation of both ras and src proto-oncogenes, and allelic deletion events involving inactivation of putative regulatory genes, including p53. To evaluate the contribution of each of these events to colon carcinogenesis, it is desirable to establish epithelial cell lines representing different stages of neoplastic progression. Such in vitro models can be used to establish a primary role for different genes implicated in neoplastic transformation, identifying events involved in multistep carcinogenesis and delineating the factors modulating cellular transformation. We present herein a summary of such an in vitro model for colon carcinogenesis using the introduction of relevant genetic elements into normal mucosa to identify the molecular steps and accompanying cellular events underlying neoplastic progression in the colon.
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PMID:Oncogene-mediated transformation. An in vitro model for colon carcinogenesis. 174 51

In a study of the mechanisms involved in the induction of tumours by chemicals, the Ha-ras oncogene was analysed in liver tumours induced by the genotoxic carcinogen diethylnitrosamine (DEN), or the non-genotoxic agent phenobarbitone (PB) in C3H/He mice. Mutations were detected using the polymerase chain reaction and oligonucleotide hybridization. Codon 61 mutations were detected in 41% of DEN-induced tumours (19/46), either in the first base (CG----AT, 12/19), a transversion, or the second base (AT----GC, 7/19), a transition. Codon 61 mutations were also found in 29% of spontaneous tumours (all CG----AT, 6/21) but none were detected in PB-induced tumours (0/15) or in normal liver tissue of untreated mice (0/30). No mutations were detected at codon 12. Low and variable expression of the Ha-ras gene was detected in all liver tissues with moderately raised levels (175-200%) in spontaneous, DEN and PB-induced tumours as compared to normal liver tissue. The H-ras gene was methylated to some extent in all liver tissues, with no discernible difference between the treatments. The frequency of the Ha-ras mutation at codon 61 in DEN-induced tumours is greater than in spontaneously arising tumours. This increase is not accompanied by any specific alteration in the expression or methylation of the gene. Since PB-induced tumours do not possess mutations in the Ha-ras gene at codons 12 or 61, the data suggest that the non-genotoxic agent PB induces tumours in the C3H/He mouse liver with a mechanism distinct from that of spontaneous tumours or those that result from treatment with a potent genotoxic carcinogen such as DEN.
Carcinogenesis 1991 Dec
PMID:Analysis of the Ha-ras oncogene in C3H/He mouse liver tumours derived spontaneously or induced with diethylnitrosamine or phenobarbitone. 174 36

Activation of the ras oncogene was investigated in esophageal tumors induced by methylbenzylnitrosamine (MBN) in the Sprague-Dawley rat. DNA was extracted from grossly visible carcinogen-induced tumors. H-ras and K-ras gene sequences were then amplified by the polymerase chain reaction. Point mutations in the ras genes were then identified by selective hybridization to allele-specific oligonucleotide probes. A guanine to adenine transition at the 35th nucleotide in the H-ras coding sequence (GGA to GAA in the 12 codon) was observed in 67% (10 of 15) of the papillomas examined. This mutation codes for glutamate instead of glycine as the 12th amino acid of the ras p21 protein. No other H-ras or K-ras mutations were observed. To determine the distribution of this H-ras mutation in esophageal tissues, histological sections of MBN-treated esophagi were stained with a monoclonal antibody (E184) which selectively recognizes the mutated ras p-21 with glutamate substituted for glycine as the 12th amino acid. Expression of the mutant ras p21 protein was observed in 20% of the squamous papillomas, 13.6% of hyperplastic lesions and 10% of dysplastic lesions. Thus, activation of the H-ras oncogene as a result of guanine to adenine point mutation is a frequent event in esophageal tumors induced by MBN, occurring in 67% of squamous papillomas, but expression of the corresponding mutant ras p21 protein is observed in a much smaller proportion of the tumors in this animal model.
Carcinogenesis 1991 Dec
PMID:Incidence of Harvey ras oncogene point mutations and their expression in methylbenzylnitrosamine-induced esophageal tumorigenesis. 174 41

Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. We have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbezanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. We found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel K-ras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation.
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PMID:ras activation in human tumors and in animal model systems. 177 91

The use of the mouse skin multistage model of carcinogenesis has aided our understanding of critical target genes in chemical carcinogenesis. The mutagenic activation of the Harvey-ras proto-oncogene has been found to be an early event associated with the initiation of mouse skin tumors by the polycyclic aromatic hydrocarbon 7,12 dimethylbenz[alpha]anthracene and the pure initiator ethyl carbamate (urethane). In contrast to chemical initiation of mouse skin tumors, ionizing radiation-initiated malignant skin tumors have been shown to possess distinct non-ras transforming gene(s). Differential screening of cDNA libraries made from chemically initiated malignant skin tumors has been used to identify a number of cellular gene transcripts that are overexpressed during mouse skin tumor progression. These differentially expressed genes include beta-actin, ubiquitin, a hyperproliferative keratin (K6), a gene whose product is a member of a fatty acid or lipid-binding protein family, and a gene called transin or stromelysin. The overexpression of the stromelysin gene, which encodes a metalloproteinase that degrades proteins in the basement membrane, is hypothesized to play a functional role in malignant tumor cell invasion and metastasis. We believe that the cloning, identification, and characterization of gene sequences that are differentially expressed during tumor progression could lead to the discovery of gene products that either play functional roles in skin tumor progression or in the maintenance of various progressive tumor phenotypes.
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PMID:Differential gene expression during multistage carcinogenesis. 177 1

Amplification and activation of c-Ki-ras gene was studied in normal human pancreas and a cell line (T-3) derived from normal pancreas explants exposed to methylnitrosourea (MNU) for 26 weeks. Normal genomic DNAs from pancreas and derived cell lines showed no transforming activity in NIH 3T3 cells. However, DNAs isolated from tumorigenic cell line derived from MNU treated human pancreas explants transformed NIH 3T3 cells. The hybridization profiles showed that the c-Ki-ras gene was amplified 5 fold in the tumorigenic cells (T-3). The level of mRNA specific to the c-Ki-ras gene was found to be 50-60 fold higher in the malignant cells than in normal human pancreas. These results suggest that higher expression of ras genes is due to gene amplification and/or activation, which is an important step in carcinogenesis.
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PMID:Amplification and activation of c-Ki-ras oncogene in cell line developed from human pancreas explants. 178 90

A high frequency of point mutations at codon 12 of the Ki-ras gene has previously been reported for rat kidney mesenchymal tumors induced by methylating N-nitroso compounds. In this study, we analyzed renal tumors with divergent histogenesis, i.e., mesenchymal tumors (sarcomas), cortical epithelial tumors (carcinomas), and embryonal tumors (nephroblastomas). Renal mesenchymal tumors and carcinomas were induced in juvenile or young adult Wistar rats by a single dose of N-nitrosodimethylamine (NDMA) while nephroblastomas were induced in Nb hooded rats by a single transplacental dose of N-nitrosoethylurea (NEU). Nephroblastomas developing spontaneously in WAB/Not rats were also examined. Amplification of Ki-ras sequences from formalin-fixed, paraffin-embedded tissue by the polymerase chain reaction was followed by direct DNA sequencing. GGT----GAT point mutations at codon 12 of the Ki-ras gene were found in 9 of 12 (75%) renal mesenchymal tumors and in 9 of 12 (75%) cortical epithelial tumors induced by NDMA. Even higher incidences were observed in nephroblastomas (8/8; 100%) induced by NEU and in spontaneous nephroblastomas (10/11; 91%). These results indicate that Ki-ras mutations are frequent events during the development of kidney tumors irrespective of their histogenesis and suggest that they may play an important role in renal carcinogenesis in rats. These data further indicate that mutational activation of Ki-ras proto-oncogenes in carcinogen-induced rat kidney tumors occurs in a tissue-specific, rather than cell-specific, manner.
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PMID:Ki-ras mutations in spontaneous and chemically induced renal tumors of the rat. 179 84

Expression of protooncogenes c-myc, N-myc, c-fos, Ha-ras 1, Ki-ras 2, yes, abl, src, N-ras, met and mos was studied in human gastric tumors and in rat gastric mucosal membrane during gastric carcinogenesis induced in rats by means of N-methyl-N'-nitro-N-nitroso guanidine (MNNG). Elevated expression of protooncogenes c-myc, c-fos, Ha-ras 1, Ki-ras 2, N-myc and Raf 1 was observed in carcinomas of human stomach. Amplification of Ha-ras 1 protooncogene was found in the human gastric tumor and metastasis. Point mutation was not detected in 12 the codon of Ha-ras I protooncogene. Expression of these protooncogenes was not altered during gastric carcinogenesis induced by MNNG in rats. However, within early steps of cancerogenesis (9 days, 3 months) amplification of ribosomal genes occurred in rat gastric mucosal membrane and in adenocarcinoma developed, while the tumor growth was accompanied by activation of mitochondrial genes.
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PMID:[Biochemical and molecular biological aspects of stomach cancer development in human and animal]. 181 23


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