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)

Loss of heterozygosity (LOH) on chromosome 13q is one of the most common genetic alterations in hepatocellular carcinoma (HCC) and might be involved in liver cancer development through inactivation of tumour suppressor genes. In order to narrow down the region of 13q loss, we examined the pattern of loss of heterozygosity (LOH) in tumours from 88 HCC patients, using 18 microsatellite markers on 13q. Thirty-eight of the 88 tumours (43%) showed LOH for at least one marker. Of these, two tumours (5%) showed 13q whole arm allelic loss, while the remaining 36 tumours (95%) had partial allelic loss. The LOH pattern defined by the 36 tumours suggested the existence of at least three different smallest common deleted regions which might be involved in the carcinogenesis of HCC. The first, the most centromeric in the 13q12.3 is, close to the BRCA2 gene, defined by D13S171; the second, the most telomeric region in the 13q31-32 band, is defined by D13S154 and D13S157; the third, the intermediate region at 13q14.3, which is near the RB gene, is defined by loci D13S268. The rate of LOH at 13q31-32 was significantly higher in Hepatitis B-surface antigen (HBsAg)-positive patients than HBsAg-negative HCC patients, pointing to a candidate gene related to the development of HBsAg-positive HCCs.
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PMID:Loss of heterozygosity at chromosome 13q in hepatocellular carcinoma: identification of three independent regions. 1067 21

In this study, we describe two renal cell carcinomas (RCC) that occurred at the same time in two brothers, yielding information on the carcinogenic process. We used flow cytometry (FCM) to evaluate nuclear DNA content, and performed cytogenetic analysis. We also carried out fluorescence in situ hybridization (FISH) with a panel of centromeric probes for chromosomes 3, 7, 8, 9, 12, 17, 20, and Y in interphase cells. Flow cytometry analysis revealed diploid histograms in the tumor and "nonmalignant" samples of patient 1, while an aneuploid cell subpopulation was found in the tumor and "nonmalignant" samples of patient 2. Tumor samples from the two brothers were studied by FISH, and had common numerical chromosome aberrations: trisomy of chromosomes 3 and 7, and monosomy and trisomy of chromosomes 9 and 17. Moreover, in normal samples from both brothers, we found monosomy 9, and in a normal sample from patient 1, monosomy 17. Cytogenetic analysis revealed trisomy 3 in some cells grown from normal kidney tissue of each brother. The identification of the same chromosome alterations in both brothers appears to provide evidence of an unusual process of carcinogenesis, probably due to a common genetic basis.
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PMID:Unusual chromosome patterns of renal cell carcinomas common to two brothers. 1068 43

The 9p21-23 chromosome region harbors a number of known and putative tumor-suppressor genes (TSGs). The best characterized gene in this area is p16(INK4A) (CDKN2A). Alterations of its product have been observed in various malignancies, including non-small-cell lung carcinomas (NSCLCs). We earlier investigated the mechanisms underlying p16(INK4A) inactivation. In the present study, we examined, in a series of 87 NSCLCs, its relationship with the kinetic parameters [proliferation index (PI) and apoptotic index (Al)] and the ploidy status of the tumors. In addition, we extended our previous LOH analysis of the 9p21-23 region by examining flanking areas of p16(INK4A). Aberrant p16 expression was observed in 41.4% of the carcinomas. A significant association was found with increased PI (p = 0.037), but not with apoptosis. Aneuploid tumors were more frequently correlated with abnormal p16 staining (p = 0. 05). A high frequency of allelic imbalance (Alm) was noticed at the D9S161 (51.3%) and D9S157 (64.5%) loci, which lie approximately 4cM centromeric and 7cM telomeric, respectively, to CDKN2A. Abnormal p16(INK4A) expression was strongly correlated with Alm at D9S161 (p = 0.004). Allelic losses at D9S157 occurred more frequently in early stages (p = 0.018) and were significantly associated with deletions at D9S161 (p = 0.035). We conclude that, in a sub-set of NSCLCs, (i) abnormal p16 expression contributes to tumor growth mainly by increasing the proliferative activity in the initial stages of carcinogenesis; (ii) the association with aneuploidy merely reflects the impact of aberrant p16 on proliferative activity; and (iii) other putative TSGs possibly reside within the 9p21-23 region that possibly co-operate in certain cases with CDKN2A in the development of NSCLCs.
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PMID:Expression of p16(INK4A) and alterations of the 9p21-23 chromosome region in non-small-cell lung carcinomas: relationship with tumor growth parameters and ploidy status. 1075 90

Telomerase is a ribonucleoprotein enzyme that catalyses the addition of telomeric repeats to telomeres. Since the shortening of telomeres is thought to act as a mitotic clock, activation of telomerase is crucial for the continued growth of cancer cells. Telomerase is frequently activated in premalignant and malignant skin tumors and even in normal skin from sun-exposed sites. Normal epidermis contains a subpopulation with telomerase activity, although those might not be stem cells. Telomerase activity correlates closely with the expression of human telomerase catalytic subunits. The effects of acute and chronic UV exposure on telomerase activity and their mechanisms should be studied in relevance to UV-carcinogenesis and photoaging.
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PMID:Telomerase in cutaneous carcinogenesis. 1076 90

Telomerase activity is known to be implicated both in cell immortalization and carcinogenesis. Telomerase activity has not been detected in most human somatic tissues. However, we previously confirmed that the activity is present both in methylazoxymethanol acetate-induced rat colonic adenocarcinoma and non-treated colonic mucosa, presumably indicating the tissue-specific activity of the enzyme in rats. To determine the standard activity of rat telomerase in various organs in relation to differences in sex, age and strain, we examined the activity by using the telomeric repeat amplification protocol (TRAP) assay. The testis, liver, and colon mucosa showed the activity. The brain had very low or negative activity in 5-week-old male rats of the F344, SD, Wistar, Donryu or ACI strains. Age (5-week-old and 9-month-old) or sex difference for the activity was not apparent in rats of these strains. In general, telomerase activity in the fetal brain, liver and kidney was stronger than in the adult organ. The telomerase activity of each organ was different from that of human. This difference may indicate that the rat has a specific mechanism for maintaining the telomeric repeats of the chromosome even in somatic tissues. The basic information resulting from this study may be useful for the study of the role of telomerase in tumorigenesis in animal experiment models.
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PMID:The telomerase activities in several organs and strains of rats with ageing. 1078 Aug 18

Telomerase is a specialized ribonucleoprotein polymerase that directs the synthesis of telomere repeats at chromosome ends. Accumulating evidence has indicated that telomerase is stringently repressed in normal human somatic tissues but reactivated in cancers and immortal cells, suggesting that reactivation of telomerase plays an important role in carcinogenesis. In this study, the status of telomerase activity in diseased human nasopharyngeal lesions was determined by the telomeric repeat amplification protocol (TRAP). Fifty-four patients participated including 17 inflammation or hyperplasia, eight with squamous metaplasia, and 29 with different stages of carcinomas. Telomerase activity was detected in 1 of 17 (5.9%) inflammatory or lymphoid hyperplastic tissues, 3 of 8 (37.5%) squamous metaplastic, and 25 of 29 (86.2%) carcinoma tissues. The differences in telomerase expression in these groups is statistically significant (P < 0.001). Levels of telomerase activity correlated with tumour stage (P = 0.024). These results suggest that telomerase reactivation plays a role in the carcinogenesis of nasopharyngeal cancer. Since telomerase activity is found in the majority of nasopharyngeal cancers and a subset of metaplasia, this enzyme may be served as a reference to monitoring the status of abnormal nasopharyngeal tissues.
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PMID:Telomerase activity is frequently found in metaplastic and malignant human nasopharyngeal tissues. 1086 2

The maintenance of telomere length has been hypothesized to be involved in the early steps of cancerogenesis. A physiologic modulation of telomere maintenance is exerted by TRF1 (telomeric-repeat binding factor-1), which deletion permits telomere elongation. Gastrointestinal neoplastic (n=19) and non-neoplastic tissues (six inflammatory disease and six normal mucosa distant from tumor at least 5 cm) were studied, by immunohistochemistry, for TRF1 expression, by using a polyclonal antibody anti-TRF1. Differentiated and not proliferating epithelial secretory cells (Ki67 and p53 negative cells) were stained by anti-TRF1, which did not stain tumor cells in all cases but one (p<0.0001). p53 was expressed by 26% of tumor cases. Inflammatory gastrointestinal non-tumor tissues showed lower expression of TRF1 in epithelial secreting cells compared to normal tissues (p=0.008). These preliminary data suggest that down-regulation of the TRF1 expression in tumor cells may be involved in cell immortalization as an initial step in gastrointestinal carcinogenesis (before p53 alteration), and may open new perspectives, when confirmed, in gastrointestinal tumor prognosis.
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PMID:Immunohistochemical telomeric-repeat binding factor-1 expression in gastrointestinal tumors. 1094 27

Major advances have been made in understanding the role of telomerase in cellular immortalization and carcinogenesis. Human telomeres undergo progressive shortening with cell division, and critical shortening of telomeres with cellular aging triggers a signal for cells to stop dividing and senesce. Telomerase is an enzyme that adds telomeric-repeated sequences to the ends of human chromosome DNA. Telomerase is active in the vast majority of tumors, but not in normal somatic tissues, and prevents progressive shortening of telomeres with cell division, probably giving tumor cells a growth advantage over normal cells. Highly-sensitive PCR-based TRAP (telomeric repeat amplification protocol) assay provided the means to analyze telomerase in a wide variety of tissues. Evidence has been accumulated that this assay may be useful as a potential diagnostic tool for cancer. The constituents of telomerase complex have recently been identified, and human telomerase reverse transcriptase (hTERT) has been found to be responsible for the enzymatic activity of telomerase. Detection of hTERT mRNA may therefore be useful for the screening and diagnosis of cancers. The mechanisms regulating hTERT expression have been extensively analyzed, and transcriptional regulation of hTERT has been found to be essential for hTERT expression, in which several nuclear factors including c-Myc play crucial roles. Understanding of such mechanisms might provide insight into molecular basis of human carcinogenesis and contributes to the development of novel cancer gene therapy targeting telomerase.
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PMID:Telomerase activity in cancer as a diagnostic and therapeutic target. 1096 25

Amplification of proto-oncogenes associated with their over-expression is one of the critical carcinogenic events identified in human cancer cells. In many cases of human gastric cancer, a proto-oncogene ERBB-2 is co-amplified with CAB1 genes physically linked to ERBB-2, and both genes are over-expressed. The amplified region containing ERBB-2 and CAB1 was named 17q12 amplicon from its chromosomal location. The syntenic region corresponding to the 17q12 amplicon is well conserved in mouse. In this study we isolated and characterized a novel mouse gene that locates telomeric to the mouse syntenic region. Northern blot analysis using the mouse cDNA and a cloned partial cDNA of human homolog disclosed a unique expression pattern of the genes. They are expressed predominantly in the gastrointestinal (GI) tract and in the skin at a lower level. Moreover, in the GI tract, the expression is highly restricted to the esophagus and stomach. Thus, we named the mouse gene Gasdermin (Gsdm). This is the first report of a mammalian gene whose expression is restricted to both upper GI tract and skin. Interestingly, in spite of its expression in normal stomach, no transcript was detected by Northern blot analysis in human gastric cancer cells. These data suggest that the loss of the expression of the human homolog is required for the carcinogenesis of gastric tissue and that the gene has an activity adverse to malignant transformation of cells.
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PMID:Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells. 1096 28

To clarify the important role of the tumor-suppressor gene p53 in maintaining genetic integrity, we estimated chromosome instability and staining of overexpressed p53 protein in the same cells of five primary breast carcinomas. The method included both fluorescence immunohistochemistry and fluorescence in situ hybridization (FISH) on sections from formalin-fixed, paraffin-embedded breast cancer tissue. By using a centromeric FISH probe for chromosome 17 on interphase cells in these sections, we showed that cells with abnormal p53 protein expression had a statistically significant higher number of chromosome 17 than did cells with no p53 protein staining in the same samples as well as cells in four other tumor samples with no p53 protein staining. The samples identified positive for p53 abnormality by immunostaining were shown to have p53 mutation by constant denaturing gel electrophoresis analysis and DNA sequencing. These mutated samples were characterized by high DNA index, high S-phase, abnormal karyotype, and aneuploidy. The results strongly implicate p53 mutation as a cause for chromosomal instability and a crucial step in mammary carcinogenesis.
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PMID:p53 abnormality and chromosomal instability in the same breast tumor cells. 1106 99


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