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)

In the course of our study on the amplification of 11q13 sequences in human breast cancer, we have investigated the amplification status of the anonymous DNA fragment D11S97 in a series of 125 mammary tumors. Our results indicate that, as with bladder carcinomas, D11S97 can be amplified separately from BCL1. In addition, we have shown that D11597 is physically linked to both D11S146 and BCL1, and is less than 100 kb centromeric to the D115146. These results indicate that, in addition to other 11q13 loci, sequences located approximately 500 kb centromeric from BCL1 could contribute to carcinogenesis of epithelial cells in vivo.
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PMID:Amplification of 11q13 DNA sequences in human breast cancer: D11S97 identifies a region tightly linked to BCL1 which can be amplified separately. 156 70

BALB/c-3T3 cells have been isolated that are resistant to NiCl2. The degree of resistance is directly dependent upon the NiCl2 exposure concentration and ranges from 6- to 11-fold. Resistance to NiCl2 does not appear to be due to alterations in cellular uptake, since the entry of Ni(II) into wild-type or resistant cells was similar. Resistance does not appear to be due to alterations in metallothionein expression. Resistant cells have a high incidence of heterochromatic abnormalities involving fusions at the centromeres as determined by C-banding and in situ hybridization utilizing a cloned mouse satellite DNA probe. Cells retain nickel resistance for many generations in the absence or presence of NiCl2 selection; however, with time in the absence of NiCl2, the level of resistance decreases. This loss of resistance is associated with a decreased number of centromeric fusions. These results indicate that nickel resistance is involved with changes in heterochromatin and suggest that this effect of nickel on heterochromatin may be important as an early step in nickel carcinogenesis.
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PMID:Characterization of mouse cell lines resistant to nickel(II) ions. 318 93

A survey of 343 break points that lead to chromosome #1 abnormalities in 218 human neoplasms showed that 49.9% were located in or immediately adjacent to the centromeric heterochromatin. Amongst rearrangements with breaks in bands p 12-q21 were 27 isochromosomes, 22 translocations of the long arm, and four translocations of the short arm to the heterochromatic regions of other chromosomes, and 35 deletions resulting in chromosomes consisting mainly or solely of one arm. Deletions following breakage at various sites in the short arm of chromosome #1 are frequent in malignancies and are quite often found in cells that are trisomic for the long arm. It is suggested that fragility of chromosomes generated as a result of early events in carcinogenesis may be one source of chromosome rearrangements, including those of chromosome #1, on which selection can operate and give rise to progressively more malignant clones.
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PMID:Break points in chromosome #1 abnormalities of 218 human neoplasms. 731 74

o-Phenylphenol (OPP) and its sodium salt, sodium o-phenylphenate are broad spectrum fungicides and disinfectants with widespread usage. Both chemicals have been reported to induce cancer in the kidney and urinary bladder of Fischer 344 rats. Recently it has been proposed that the metabolic activation of OPP occurs via a two-step process involving the cytochrome P450-mediated formation of phenylhydroquinone (PHQ) in the liver and a prostaglandin H synthase-mediated oxidation of PHQ to phenylbenzoquinone (PBQ) in the urinary tract. In order to further investigate the metabolic activation and genotoxic effects of OPP, we have investigated the ability of PHQ and PBQ to induce micronuclei and mutations at the HGPRT locus in a prostaglandin H synthase-containing V79 Chinese hamster lung fibroblast cell line. In arachidonic acid-supplemented V79 cells, PHQ induced a significant increase in micronuclei whereas no increase was observed in cells in the absence of arachidonic acid supplementation. Immunofluorescent labeling of centromeric proteins with the CREST antibody indicated that the arachidonic acid-dependent induction of micronuclei by PHQ was due almost entirely to micronuclei containing whole chromosomes which had failed to segregate properly during mitosis. The induction of micronuclei by PHQ was significantly inhibited by treatment of the cells with indomethacin, aspirin, ascorbic acid, dithiothreitol and reduced glutathione supporting a role for prostaglandin H synthase in the genotoxic effects of PHQ. No increase in 6-thioguanine-resistant cells was observed in cells treated with PHQ or PBQ. This arachidonic acid-dependent conversion of PHQ to a genotoxic species is consistent with the hypothesis that a prostaglandin H synthase-mediated activation of PHQ may be involved in OPP- and SOPP-induced urinary tract carcinogenesis and also suggests that the induction of aneuploidy may play an important role in OPP-induced tumorigenesis.
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PMID:Genotoxic effects of the o-phenylphenol metabolites phenylhydroquinone and phenylbenzoquinone in V79 cells. 752 18

The purpose of our study was to detect somatic changes in renal cell carcinoma by multilocus fingerprinting. DNA fingerprints were generated from the DNA of normal and malignant renal tissue samples of 29 patients with nonhereditary kidney carcinoma by using oligonucleotide probes specific for simple repeat motifs such as (GTG)5, (CA)8, (GACA)4, or (TTAGGG)3. Each probe rendered a typical fingerprint pattern, because it is specific with respect to the target regions recognized in the genome. The restriction enzymes used were HinfI and HaeIII. Changed banding patterns were detected by using (GTG)5 in 20% of the tumors, in 20% for (CA)8 after HinfI digestion, and in 10% after HaeIII digestion. Even more informative probes were (GACA)4, showing 70% changes after HaeIII digestion, and (TTAGGG)3, with 80% changes after digestion with either enzyme. Since the simple repeat motifs recognized by (GACA)4 are localized on the short arms of the acrocentric chromosomes (13, 14, 15, 21, and 22), it is possible that sequences important for renal carcinogenesis are present in these regions. The observation of changes in regions to which (TTAGGG)3 hybridizes points to an involvement of DNA elements in telomeric sequence related regions in human kidney tumor formation.
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PMID:Detection of somatic changes in human renal cell carcinomas with oligonucleotide probes specific for simple repeat motifs. 766 46

Centromere spreading (CS) of chromosomes and high occurrence of aberrations at centromeric region were observed in two papillary serous cystadenocarcinomas and one borderline papillary serous cystadenoma of the ovary. In the borderline tumor, CS of chromosome 12, trisomy of which had been reported as the sole abnomaly in benign ovarian tumors, was seen in three metaphases. It is suggested that CS may be an early event in the carcinogenesis of epithelial ovarian tumors. Centromeres of some chromosomes in tumor cells may be unstable and thus bring about premature centromere separations and breakages at centromeric regions, followed by some numerical and structural chromosomal aberrations.
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PMID:Centromere spreading and centromeric aberrations in ovarian tumors. 769 35

Tumor suppressor genes have been found to have loss of function in a number of malignancies. This loss of function is believed to contribute to malignant transformation or metastatic spread. In the present study, expression of the retinoblastoma (RB) tumor suppressor gene was examined in cell lines and tumor tissue obtained from primary renal and metastatic sites in patients with metastatic renal cell carcinoma. Three of fifteen (20%) of informative renal carcinoma cell lines had loss of heterozygosity (LOH) in the RB gene (intron 20) detected by polymerase chain reaction analysis. Using restriction fragment length polymorphism (RFLP) analysis, 7 of 22 (32%) informative cell lines had LOH centromeric to the RB gene at the D13S1 locus. No LOH (0 of 7) was seen telomeric to the RB gene at the D13S2 locus. None of the 28 cell lines examined had decreased RB mRNA expression compared with short-term cultures of proximal renal tubular cells. Western blotting demonstrated phosphorylated and unphosphorylated forms of RB protein of expected molecular weight in all 41 cell lines (33 primary and 8 metastatic) examined. Twenty-nine primary cell lines and 6 metastatic cell lines all demonstrated normal immunohistochemical staining. Loss of RB immunohistochemical staining in paraffin-embedded tissue was detected in none of the primary tumors (0 of 30) or metastatic tumors (0 of 12). The absence of abnormalities of RB expression detected in these renal cell carcinomas suggests that abnormalities of the RB gene are not central to malignant transformation or progression in this tumor type; however, another tumor suppressor gene centromeric to the RB locus may be important in renal cell carcinogenesis.
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PMID:Loss of heterozygosity occurs centromeric to RB without associated abnormalities in the retinoblastoma gene in tumors from patients with metastatic renal cell carcinoma. 775 92

Shortening of telomeres may contribute to the control of the proliferative capacity of normal cells, and telomerase, the enzyme that elongates telomeric DNA, may be essential for unlimited cell proliferation. We have shown previously that telomerase activity is present in human cells immortalized in vitro and in metastatic ovarian carcinoma cells but is undetectable in normal cultured cells or normal tissues. We have determined the temporal pattern of telomerase activity during colorectal carcinogenesis in man. We report that telomerase activity is associated with acquisition of malignancy as it is detectable in colorectal carcinoma but not in adenomatous polyps. Mutations leading to reactivation or upregulation of the enzyme may represent an additional required event in the multistep development of colorectal cancer.
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PMID:Telomerase activity associated with acquisition of malignancy in human colorectal cancer. 778 Sep 64

Four disease genes (NBCCS, ESS1, XPAC, FACC) map to 9q22.3-q31. A fine map of this region was produced by linkage and haplotype analysis using 12 DNA markers. The gene for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin) has an important role in congenital malformations and carcinogenesis. Phase-known recombinants in a study of 133 meioses place NBCCS between (D9S12/D9S151) and D9S176. Haplotype analysis in a two-generation family suggests that NBCCS lies in a smaller interval of 2.6 cM centromeric to D9S287. These flanking markers will be useful clinically for gene tracking. Recombinants also map FACC (Fanconi anemia, group C) to the same region, between (D9S196/D9S197) and D9S287. The recombination rate between (D9S12/D9S151) and D9S53 in males is 8.3% and 13.2% in females, giving a sex-specific male:female ratio of 1:1.6 and a sex-averaged map distance of 10.4 cM. No double recombinants were detected, in agreement with the apparently complete level of interference predicted from the male chiasmata map.
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PMID:Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3. 783 1

Chromosomal region 8p11.2-p12 is consistently amplified in human breast cancer. We have constructed a 2.8 Mb YAC contig of this region, centered on the human Fibroblast Growth Factor Receptor 1 (FGFR1) locus and encompassing the Adrenergic beta 3 Receptor (ADRB3) locus. A smaller centromeric YAC contig spanning 1.4 Mb was also assembled, and included the Ankyrin 1 (ANK1) and Tissue-type Plasminogen Activator (PLAT) genes. Results from mapping of the contigs showed physical linkage of the ADRB3 and FGFR1 genes, which were colocalized within the same YAC clone and separated by about 900 kb, FGFR1 being in centromeric position. It also showed physical linkage of ANK1 and PLAT genes, which appear to be separated by a maximum of 700 kb. In parallel, several loci were mapped according to their amplification status in a large panel of breast tumor samples. The overall amplification pattern suggested a continuous amplicon with a core around FGFR1. Data from both the detailed physical map and the amplification status allowed to establish the following gene order, from telomere to centromere: ADRB3-D8S105-FGFR1-ANK1-PLAT-POLB. The precise localization and YAC cloning of the core of the amplicon will allow to isolate a putative oncogene involved in mammary carcinogenesis.
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PMID:Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma. 789 40


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