Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C-erbB-2 and epidermal growth factor receptor (EGFR) genes were independently shown to be associated with breast cancer progression. In this report, we have analyzed the structure and expression of these 2 genes in the same tumor specimens of a large series of breast cancers. Two clinical types of tumor were studied: inflammatory (IBC) and non-inflammatory breast cancers (NBC) obtained from 221 untreated patients at different clinical stages. Amplification and over-expression of the c-erbB-2 proto-oncogene were observed in 27% and 47% of tumors, respectively, and were strongly associated with breast cancers of the most unfavorable prognosis, namely IBC and NBC with multiple positive axillary nodes. EGFR gene was neither amplified nor rearranged. A restriction fragment length polymorphism (RFLP) for HindIII endonuclease was observed. EGFR transcripts were detected in 46% of tumors and observed more frequently in IBC than in NBC (p less than 0.02). In NBC the presence of EGFR transcripts increased linearly with lymph-node involvement and was associated with estrogen-receptor-negative tumors (p = 0.01). Analysis of both genes from the same tumor samples indicated that genes are associated with cancer aggressiveness. Furthermore, in NBC these 2 genes were independently activated, in contrast to IBC in which activated genes were negatively correlated, suggesting that c-erbB-2 and EGFR genes play different roles in NBC and IBC.
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PMID:Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance. 256 19

The hrp gene cluster of strains of Xanthomonas campestris that cause diseases of citrus was examined by Southern hybridization of genomic DNA and by restriction endonuclease analysis of enzymatically amplified DNA fragments of the hrp gene cluster. The hrp genes were present in all strains of the pathovars of X. campestris tested in this study, including strains of the three aggressiveness groups of the citrus bacterial spot pathogen, X. campestris pv. citrumelo. X. campestris pv. citri strains in groups A, B, and C, which cause citrus canker A, B, and C, respectively, each produced characteristic restriction banding patterns of amplified hrp fragments. The restriction banding patterns of all strains within each group were identical. In contrast, restriction fragment length polymorphism was evident among strains of the moderately and weakly aggressive groups of X. campestris pv. citrumelo. X. campestris pv. citrumelo strains in the highly aggressive group had a homogeneous restriction banding pattern. The characteristic banding patterns obtained for each bacterial group indicate that X. campestris strains causing disease in citrus can be reliably differentiated and identified by restriction analysis of amplified DNA fragments of the hrp gene cluster. In addition, the phylogenetic analysis based on the restriction banding patterns of amplified fragments suggests a polyphyletic relationship of the hrp genes among the strains of X. campestris that cause disease in citrus.
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PMID:Genetic analysis of hrp-related DNA sequences of Xanthomonas campestris strains causing diseases of citrus. 791 99

Medulloblastoma is the most common malignant brain tumor in children. Chromosome arm 17p13.3 is reduced to homozygosity in 35-50% of medulloblastomas,making it the most frequent genetic alteration in these tumors. HIC-1 (hypermethylated in cancer) is a putative tumor suppressor gene located in the area of common deletion. HIC-1 resides in a CpG island and is hypermethylated in many different tumor types. Therefore, we studied a series of tumor specimens for hypermethylation and deletion of the region containing the HIC-1 gene to determine whether these two mechanisms of gene inactivation play a complimentary role in medulloblastoma. Southern blotting was performed using the methylation-sensitive restriction endonuclease NotI. Methylation of NotI restriction sites located in HIC-1 was demonstrated in 26 (72%) of 36 tumors and 11 (92%) of 12 specimens of normal brain. Of these 26 tumors, 23 differed significantly from normal brain. A greater proportion of the cells from the tumors showed methylated alleles of the HIC-1 gene. A group of 15 (42%) of 36 tumors exhibited loss of heterozygosity (LOH) for DNA sequences located on chromosome arm 17p. There was no significant correlation between LOH and methylation status (P = 0.19). Methylation in tumors beyond that seen in normal brain predicted poor overall survival independent of clinical risk category (P = 0.014). The results of our study show that methylation of the CpG island that contains the HIC-1 gene is common in medulloblastoma and, together with LOH of 17p, may be a critical event in the formation and aggressiveness of this tumor.
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PMID:Hypermethylation of HIC-1 and 17p allelic loss in medulloblastoma. 1209 91

Traditional morphological methods of Meloidogyne identification have been unsuccessful in distinguishing three South Carolina, USA Meloidogyne arenaria race 2 populations-Govan, Pelion, and Florence. These populations differ greatly in reproductive rate and aggressiveness on soybean hosts. Total genomic DNA from eggs of each population was digested with the restriction endonuclease Eco RI and Southern hybridization analyses were performed with single-copy and interspersed multi-copy cloned probes. Probes were isolated from a genomic library of Eco RI, M. arenaria DNA fragments cloned into pUC8. One probe, designated pE1.6A, when hybridized to Southern blots of M. arenaria genomic DNAs, displayed an interspersed repetitive pattern, and the RFLPs distinguished the Govan population from the Pelion and Florence populations. Another clone, pE6.0A, carrying moderately repeated sequences, distinguished the Pelion and Florence isolates. This communication demonstrates the utility of genomic RFLP analysis for distinguishing populations of the same race within the same species. To test the possible utility of these moderately repeated sequence probes for detecting the presence of nematode DNA in DNA samples from roots inoculated with varying numbers of nematodes, dot blot hybridization analyses were performed. It is possible to detect as few as 30 nematodes per root sample with these cloned probes.
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PMID:Genomic RFLP Analysis of Meloidogyne arenaria Race 2 Populations. 1928 97

The apurinic/apyrimidinic endonuclease 1 (APE1) is a protein central to the base excision DNA repair pathway and operates in the modulation of gene expression through redox-dependent and independent mechanisms. Aberrant expression and localization of APE1 in tumors are recurrent hallmarks of aggressiveness and resistance to therapy. We identified and characterized the molecular association between APE1 and nucleophosmin (NPM1), a multifunctional protein involved in the preservation of genome stability and rRNA maturation. This protein-protein interaction modulates subcellular localization and endonuclease activity of APE1. Moreover, we reported a correlation between APE1 and NPM1 expression levels in ovarian cancer, with NPM1 overexpression being a marker of poor prognosis. These observations suggest that tumors that display an augmented APE1/NPM1 association may exhibit increased aggressiveness and resistance. Therefore, targeting the APE1/NPM1 interaction might represent an innovative strategy for the development of anticancer drugs, as tumor cells relying on higher levels of APE1 and NPM1 for proliferation and survival may be more sensitive than untransformed cells. We set up a chemiluminescence-based high-throughput screening assay in order to find small molecules able to interfere with the APE1/NPM1 interaction. This screening led to the identification of a set of bioactive compounds that impair the APE1/NPM1 association in living cells. Interestingly, some of these molecules display anti-proliferative activity and sensitize cells to therapeutically relevant genotoxins. Given the prognostic significance of APE1 and NPM1, these compounds might prove effective in the treatment of tumors that show abundant levels of both proteins, such as ovarian or hepatic carcinomas.
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PMID:Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties. 2586 59