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 prostate tumor-inducing gene 1 (PTI-1) transcript is detected in various human carcinoma cells. PTI-1 is reported to consist of a 5' untranslated region (5' UTR) homologous to mycoplasma 23S rRNA and a coding region corresponding to a truncated and mutated form of the translation elongation factor 1A, eEF1A. We have found that the PTI-1 transcript may encode a truncated, but not mutated, form of the human isoform eEF1A1. Additionally, the 5' UTR sequence of PTI-1 from genomic DNA of different cell lines and blood samples varies from the original sequence. This 5' -UTR region of PTI-1 presents a fusion of E. coli and Mycoplasma hyorhinis 23S rRNA. We have overexpressed the potential PTI-1 protein in E. coli and various human cell lines. The resulting protein could be detected by western blotting using anti-eEF1A antibodies. However, we were unable to detect the PTI-1 protein in LNCaP cell extracts. The potential roles of the PTI-1 protein in carcinogenesis and the origin of the PTI-1 gene in the human genome are discussed.
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PMID:Deconstructing PTI-1: PTI-1 is a truncated, but not mutated, form of translation elongatin factor 1A1, eEF1A1. 1571 6

WNT and Hedgehog signaling pathways network together during carcinogenesis and embryogenesis. WNT7A mRNA is expressed in human gastric and pancreatic cancer cells. WNT7A mRNA expression is relatively high in the temporal, occipital and parietal lobes, paracentral gyrus of the cerebral cortex, caudate nucleus, hippocampus, medulla oblongata and putamen within the adult human brain. Here, we identified and characterized the rat Wnt7a gene using bioinformatics. The rat Wnt7a gene, consisting of four exons, was located within the AC106100.7 genome sequence. Rat Wnt7a (349 aa) with 24 Cys residues and 3 Asn-linked glycosylation sites showed 99.7, 99.1 and 93.7% total-amino- acid identity with mouse Wnt7a, human WNT7A and chicken wnt7a, respectively. The N-terminal signal peptide was not identified within the Wnt7a orthologs. Exonic regions, except the 3'-UTR, were conserved between the rat Wnt7a and human WNT7A genes; however, the 5'-flanking region was significantly divergent between the rat Wnt7a and human WNT7A genes. Although the COMP1- and ELK1-binding sites within exon 1 were conserved among mammalian Wnt7a promoters, transcriptional regulation of the rodent Wnt7a orthologs was predicted to be distinct from that of human WNT7A based on the divergence within the 5'-flanking promoter region. Therefore, biological functions of rodent Wnt7a are not always consistent with those of human WNT7A due to promoter evolution. This is the first report on the rat Wnt7a gene and comparative genomics for Wnt7a orthologs.
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PMID:Comparative genomics on Wnt7a orthologs. 1575 57

Cyclooxygenases (COXs) are key enzymes that convert arachidonic acid to prostaglandins. Overexpression of COX-2, one of the COX isozymes, has been shown to be an early event in lung carcinogenesis and may play an important role in lung cancer development. A common single nucleotide polymorphism, T8473C, located within a potential functional region in the 3'UTR of COX-2 gene was identified and we hypothesized that this COX-2 variant is associated with lung cancer risk. To test this hypothesis, we genotyped this variant in a case-control study of 322 histologically-confirmed lung cancer patients and 323 age and sex frequency-matched cancer-free controls in a Chinese population. The results showed that the frequencies of variant genotypes 8473CT/CC were significantly less common in the cases (27.3%) than in the controls (35.3%) (P=0.034), suggesting that the 8473C allele was protective against lung cancer. Multivariate logistic regression analyses revealed that the COX-2 variant genotypes (8473CT/CC) were associated with a significantly decreased risk of lung cancer compared with the 8473TT wild-type homozygotes (OR=0.64, 95% CI=0.45-0.92). When we defined the reference group as non-smokers having the 8473CT/CC variant genotypes, the smokers with the 8473TT wild-type genotype had the greatest risk (adjusted OR=5.28, 95% CI=3.10-9.00). These findings indicate that the COX-2 T8473C polymorphism may contribute to lung cancer susceptibility in the Chinese population. Further larger molecular epidemiological studies are warranted to confirm these findings.
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PMID:A common polymorphism in the 3'UTR of cyclooxygenase 2/prostaglandin synthase 2 gene and risk of lung cancer in a Chinese population. 1577 67

WNT, Hedgehog and Notch signaling pathways network together during carcinogenesis and embryogenesis. WNT3A-WNT9A (WNT14) locus at chromosome 1q42.13 and WNT3-WNT9B (WNT14B) locus at chromosome 17q21.31 are paralogous regions within the human genome. WNT9A mRNA is expressed in various types of human cancer, such as gastric cancer, pancreatic cancer, and breast cancer. In addition, Wnt9a gene is implicated in chondrogenesis and joint formation during embryogenesis. Here we identified and characterized rat Wnt9a gene by using bioinformatics. Rat Wnt9a gene, consisting of four exons, was located within AC121055.4 and AC133374.2 genome sequences. Rat Wnt9a protein (365 aa) with N-terminal signal peptide, 24 Cys residues and one Asn-linked glycosylation site showed 100%, 98.1% and 82.5% total amino-acid identity with mouse Wnt9a, human WNT9A and chicken wnt9a, respectively. Exonic regions except 3'-UTR were well conserved between human WNT9A and rodent Wnt9a genes; however, 5'-flanking promoter region was not well conserved. Transcription-factor-binding sites conserved between human WNT9A and rodent Wnt9a 5'-flanking promoter regions were not identified by using the Match program. Although the amino-acid sequence was highly conserved among mammalian Wnt9a orthologs, the 5'-flanking promoter region was significantly divergent between human WNT9A and rodent Wnt9a genes. This is the first report on rat Wnt9a gene as well as on comparative genomics for Wnt9a orthologs.
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PMID:Comparative genomics on Wnt9a orthologs. 1580 69

Thymidylate synthase (TS) catalyzes the 5,10-methylene-tetrahydrofolate-mediated conversion of deoxyuridine monophosphate to deoxythymydine monophosphate, a nucleotide required for DNA synthesis and repair. The impaired TS expression has been shown to be related to 28 bp tandem repeats and a G-->C SNP in the 5'-UTR of TS. Folate deficiency has been demonstrated to play a role in gastroesophageal carcinogenesis. This case-control study was to examine the hypothesis that the TS polymorphisms, alone or in combination with serum folate status, may confer susceptibility of the hosts to gastroesophageal cancer. We analyzed TS genotype and serum folate concentration in 324 patients with esophageal squamous cell carcinoma (ESCC), 231 patients with gastric cardia adenocarcinoma (GCA) and 492 controls. It was found that compared with the normal expression TS genotype, the low expression TS genotype alone was significantly associated with increased risk of ESCC [adjusted odds ratio (OR) 1.47; 95% confidence interval (CI) 1.03-2.10] but not GCA (OR=0.98, 95% CI=0.68-1.40). More importantly, a significant interaction between the TS polymorphisms and serum folate status in risk of ESCC and GCA was observed. Among subjects with low serum folate concentration (<3 ng/ml), the ORs of ESCC and GCA for the low expression genotype were 22.63 (95% CI=10.44-49.05) and 4.08 (95% CI=1.94-8.59), which were greater than respective 9.97 (95% CI=5.67-17.53) and 1.88 (95% CI=1.18-3.24) for the normal expression genotype (P=0.002 and 0.029). These results suggest an important role for folate deficiency and impaired TS activity in the etiology of ESCC and GCA.
Carcinogenesis 2005 Aug
PMID:Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status. 1581 9

Fruits and certain vegetables have a protective effect on gastric cancer (GC) and folate is one of the nutrients in fruits and vegetables. We hypothesized that the polymorphisms of thymidylate synthase (TYMS) gene involved in folate metabolism are associated with GC risk. In a population-based case-control study of 337 GC cases and 326 controls, frequency-matched by age, sex and residential areas in a southern Chinese population, we genotyped the 28 bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and the 6 bp deletion/insertion at bp 1494 in the TYMS 3'-untranslated region (TS3'UTR). We found that although the TSER polymorphism had no main effect on GC risk, the TS3'UTR 6 bp/6 bp genotype was associated with a significantly increased risk of GC [adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.18-3.25], especially the non-cardiac gastric cancer (2.16, 1.22-3.82), compared with the 0 bp/0 bp genotype. However, when we evaluated these two polymorphisms together and used the combined genotype with zero variant allele (TSER 2R and TS3'UTR 6 bp variant alleles) as the reference, we found that the combined genotype with three or four variant alleles was associated with a significantly increased risk of GC (2.06, 1.12-3.79), especially the non-cardiac gastric cancer (2.33, 1.19-4.59), and this significant association was more pronounced among older women (>60 years old), non-smokers, and never tea drinkers. In conclusion, the TYMS polymorphisms, especially the TS3'UTR polymorphism, are associated with GC risk, especially the non-cardiac gastric cancer, and the TSER 2R and TS3'UTR 6 bp alleles may jointly play a role in the etiology of GC in the southern Chinese population. Larger studies are warranted to verify these findings.
Carcinogenesis 2005 Oct
PMID:Polymorphisms of thymidylate synthase in the 5'- and 3'-untranslated regions associated with risk of gastric cancer in South China: a case-control analysis. 1593 32

FAT10 is a member of the ubiquitin-like modifier family of proteins and has been implicated to play important roles in antigen presentation, cytokine response, apoptosis and mitosis. We have recently demonstrated the upregulation of FAT10 gene expression in 90% of hepatocellular carcinoma patients. Here, we identified and characterized the promoter of the FAT10 gene to elucidate the mechanism of FAT10 gene expression. Notably, we found that the 5' untranslated region (5'UTR), from the transcription start site to 15 bases before the translational start site, displays significant promoter activity. Regions upstream of the 5'UTR (from +26 to -1997) do not confer any promoter activity. Curiously, FAT10 promoter activity and expression is significantly repressed in KB3-1 and HepG2 cells, which have wild-type p53, than in p53-negative Hep3B cells. The role of p53 in regulating FAT10 expression was evident by the significant downregulation (P<0.05) of FAT10 mRNA expression and promoter activity when wild-type p53 was transfected into p53-null Hep3B cells. Conversely, inhibiting p53 expression through siRNA against p53 significantly enhanced FAT10 expression and promoter activity. p53 was found to bind in vivo to the 5' half consensus sequence of p53-binding site located at the FAT10 promoter. Hence, we propose that FAT10 is a downstream target of p53 and dysregulation of FAT10 expression in p53-defective cells could contribute to carcinogenesis.
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PMID:p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers. 1650 12

Tumour onset and progression are due to the accumulation of genomic lesions, which alter gene expression and ultimately proteome activities. These lesions are thought to affect primarily the transcriptional control of gene expression. In the present study, we aimed at evaluating the genome-wide occurrence of alterations in the translational control exploiting an isogenic, phenotypically validated cellular model of colorectal cancer (CRC) transition from invasive carcinoma to metastasis. In this model, microarray profiling shows that changes in the level of messenger ribonucleic acid (mRNA) association with polysomes occur more than 2-fold than changes in the level of total cellular mRNA. When common to both the total and polysomal compartments, these changes are also homodirectional, being amplified in magnitude at the polysomal level. Comparison between the transcriptional and the translational fluctuations revealed distinct signatures of statistically over-represented gene functions, involving the program of cell proliferation for both levels of analysis, while the apoptosis and the translation programs were affected mainly at translation. Looking for an upstream determinant of translational deregulation, we found an increase in the hyperphosphorylated form of the 4E-BP1 protein in the metastatic cell line, possibly resulting in an increased activation of cap-dependent translation due to increased activity of the eIF4E protein. Analysis of the distribution profiles for the 5' untranslated region (5'-UTR) length of the changed genes showed an association between longer 5'-UTRs and the probability for the relevant gene to be altered translationally, consistent with enhanced eIF4E function. This genome-wide analysis is in favour of a model of profound alteration of translational control in late CRC progression. It also suggests polysomal mRNA profiles as a new, informative dimension for the study of transcriptome imbalance in cancer.
Carcinogenesis 2006 Jul
PMID:Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis. 1653 51

Fifty single-nucleotide polymorphisms (SNPs) associated with amino acid changes in 36 genes involved in diverse DNA repair pathways were assessed for associations with risk for small cell lung carcinoma (SCLC) by a case-control study consisting of 211 SCLC cases and 685 controls. An SNP, Val83Met, in the MTH1 (microtT homolog 1) gene encoding a triphosphatase that hydrolyzes pro-mutagenic oxidized nucleoside triphosphates, such as 8-hydroxy-dGTP and 2-hydroxy-dATP, showed the strongest and a significant association with SCLC risk [odds ratio (OR)=1.6, 95% confidence interval (CI): 1.2-2.2, P=0.004], while three other SNPs in the TP53, BLM and SNM1 genes, respectively, also showed marginal associations (0.05<P<0.1). Another SNP, which causes a nucleotide change in the 5'-UTR of MTH1 transcripts leading to alternative translation initiation, was additionally examined and the SNP also showed a significant association (OR=1.7, 95% CI: 1.2-2.3, P=0.002). The two SNPs in the MTH1 gene were in linkage disequilibrium, and the OR for carrying a copy of the haplotype consisting of both the risky SNP alleles was 2.0 (95% CI: 1.2-3.2, P=0.002). The present results indicate that inter-individual differences in MTH1 activities due to SNPs are involved in susceptibility to SCLC.
Carcinogenesis 2006 Dec
PMID:Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk. 1677 34

Histone H3 lysine 9 (H3-K9) methylation and DNA methylation are important features of mammalian heterochromatin. Suppressor of variegation 3-9 homolog 2 (SUV39H2) is the histone methyltransferase that is required to methylate H3-K9, leading to transcriptional repression or silencing of target genes. In this study, we investigated the association of SUV39H2 polymorphisms and the risk of lung cancer. From the results of PCR direct sequencing, eight single nucleotide polymorphisms (SNPs) of SUV39H2 were identified in Korean population. In a hospital-based study of 346 lung cancer patients and 423 healthy controls, a novel SNP in the 3'-UTR of SUV39H2 (1624 G-->C) was associated with a statistically significant increase in lung cancer risk. Compared to the G/G genotype, genotypes with 1624C allele (G/C + C/C) significantly increased the susceptibility to lung cancer with adjusted odds ratio (AOR) of 2.63 (95% confidence interval (CI)= 1.10-6.29) for ever-smokers, especially in the older age group (age >or=55 years). Specifically, the variant genotype of 1624SNP was significantly associated with an increased risk of squamous cell carcinoma (AOR, 3.52; 95% CI = 1.13-9.45) in the older age group, while no significant association was found in patients with other histology. This study provided the first evidence that a novel SUV39H2 polymorphism may be an important predictive marker for lung cancer susceptibility for the smokers.
Carcinogenesis 2006 Nov
PMID:Novel polymorphisms in the SUV39H2 histone methyltransferase and the risk of lung cancer. 1677 42


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