Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epstein-Barr virus (EBV) encoded DNA polymerase (POL) was cloned and over-expressed in Escherichia coli. Western blot analysis confirmed the presence of antibody to this POL protein in sera from nasopharyngeal carcinoma (NPC) patients. By Western blot analysis, moderate to high concentration of IgG POL-specific antibodies were present in 43 of 48 NPC sera and only 4 of 48 healthy, seropositive controls. The POL-specific IgG antibodies appear as early as stage I of NPC, suggesting that the recombinant POL protein can be a useful diagnostic marker for early diagnosis of the disease. It was also found that human sera containing high titer of cytomegalovirus (CMV) antibodies or herpes simplex virus type 1 (HSV-1) antibodies did not cross-react with the recombinant EBV POL, despite the homology shared by DNA polymerase proteins of these viruses.
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PMID:Expression of the Epstein-Barr virus DNA polymerase in Escherichia coli for use as antigen for the diagnosis of nasopharyngeal carcinoma. 771 98

The propensity of a cell to undergo apoptosis has been proposed to be a determinant for chemotherapy sensitivity that is not directly dependent on specific drug-target interactions. Androgen-independent prostate cancer is typically refractory to cytotoxic drugs, and we tested whether this is due to a loss of the ability to undergo apoptosis. Exposure of the hormone-insensitive and p53-negative human prostate carcinoma cell line PC-3 to 22 microM cisplatin, 1 microM camptothecin, 10 microM tenoposide, 135 nM vincristine, or 10 microM lovastatin for 72 h caused cell death, internucleosomal DNA fragmentation, and morphological changes typical for apoptosis. One microM cycloheximide prevented anticancer drug-induced apoptosis, whereas high concentration (1 mM) of cycloheximide alone induced apoptosis, indicating that protein synthesis was not needed for these cells to undergo apoptosis. Since cycloheximide affected DNA synthesis and proliferation of PC-3 cells, we tested whether the DNA polymerase inhibitor aphidicolin could also suppress drug-induced apoptosis. In contrast to cycloheximide, aphidicolin inhibited only vincristine-induced apoptosis. Cycloheximide prevented drug-induced changes in cell cycle distribution except for vincristine, while aphidicolin led to an accumulation of cells at the G1-S border independent of the drug used. These data indicate that macromolecular synthesis, active cell cycling, and p53 expression are not required for apoptosis to proceed in this system.
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PMID:Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3. 774 12

The polymerase chain reaction (PCR) was used to investigate samples from Indonesian and Swedish patients with cervical intraepithelial neoplasia grade III (CIN III), squamous cell carcinoma or adenocarcinoma of the cervix for the presence of a transforming fragment (BC 24) of herpes simplex virus type 2 (HSV-2) DNA. The PCR test for HSV-2 DNA was more sensitive than the infectivity endpoint titer in a cell culture system and no cross reactivity was found with either varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human papillomavirus 16 or 18, or human genomic DNA. Using this PCR test, 2 out of 5 cases with CIN III, 10 of 71 squamous cell carcinomas, and 3 of 11 adenocarcinomas of the uterine cervix were found to contain DNA sequences homologous to the BC 24 fragment of the HSV-2 genome. Only two of the samples containing this transforming region of the HSV-2 DNA were positive in a PCR assay for the HSV-2 DNA polymerase gene. The great majority of the HSV-2 BC 24 DNA positive (12 of 15) came from the Indonesian group of patients. All 15 CIN III or cancer samples positive for the HSV-2 BC 24 fragment were also positive for papillomavirus DNA. In line with observations made by others, our data support the hypothesis that HSV infection could represent one of several possible oncogenic cofactors leading to cervical carcinoma. The HSV cofactor might be more important in the Indonesian than in the Swedish population.
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PMID:Detection of the BC 24 transforming fragment of the herpes simplex virus type 2 (HSV-2) DNA in cervical carcinoma tissue by polymerase chain reaction (PCR). 779 6

We examined the effects of a combination of adriamycin (ADR) and caffeine on DNA and protein biosynthesis and on the activities of DNA polymerase alpha and beta in normal and tumor tissue. The decrease in DNA and protein biosynthesis in tumor produced by caffeine combined with ADR were 2.5 and 2.4 times greater, respectively, compared with ADR alone. The combination of caffeine and ADR enhanced the decrease in DNA polymerases activities in the tumor which was induced by ADR, the decreases being 1.8 and 1.6 times greater, respectively, than that of ADR alone. In contrast, these ADR-induced changes in normal tissues were not enhanced by the combination with caffeine. The combination with caffeine had no effect on ADR concentration in normal tissues, but in the tumor, it increased the ADR concentration to 2.1 times that of ADR alone. In vitro, ADR efflux from Ehrlich ascites carcinoma cells was significantly inhibited by exposure to caffeine. These findings indicate that the effect of caffeine on ADR concentration in the cell plays an important role in the mechanism by which caffeine enhances ADR antitumor activity.
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PMID:Mechanism of caffeine modulation of the antitumor activity of adriamycin. 786 36

With DNA polymerase chain reaction-single strand conformation polymorphism assay followed by direct DNA sequencing, p53 gene mutation was examined in bladder transitional epithelial cell carcinoma, renal cell carcinoma and testicular seminoma. p53 gene mutation was found in 7 cases (35%) of bladder carcinoma and 4 cases (23.5%) of testicular seminoma. Inactivation of Rb gene and activation of ras and c-erbB-2 were also studied. The results suggest that development of urologic neoplasms is closely associated with p53 gene mutation and involves loss of expression of Rb and aberrant expression of ras and c-erbB-2.
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PMID:[Mechanism of p53 gene mutation in the development of urologic cancer]. 786 97

A series of selective antiherpetic compounds were found to exert pronounced cytostatic activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) thymidine kinase (TK) gene-transfected mammary carcinoma FM3A cells. Based on their potency and mechanism of cytostatic action, the antiherpetic compounds could be divided into two different classes. The first class encompasses (E)-5-(2-bromovinyl)-2'-deoxyuridine and structurally related analogues thereof [i.e., the cytosine derivative (E)-5-(2-bromovinyl)-2'-deoxycytidine and the 4'-thio derivative (E)-5-(2-bromovinyl)-2'-deoxy-4'-thiouridine]. These compounds are exquisitely cytostatic against FM3A/TK-/HSV-1 TK+ and FM3A/TK-/HSV-2 TK+ cells (50% inhibitory concentrations ranging from 0.047 to 0.001 microM) and inhibit tumor cell proliferation by inhibiting cellular thymidylate synthase. The second class consists of the acyclic guanosine derivatives penciclovir, buciclovir, and ganciclovir. These compounds are also more inhibitory to the HSV-1 TK or HSV-2 TK gene-transfected FM3A cells than to FM3A/0 or FM3A/TK- cells, but at concentrations that are higher than the concentrations at which the (E)-5-(2-bromovinyl)-2'-deoxyuridine derivatives proved to be inhibitory. These acyclic guanosine analogues appear to be targeted at the cellular DNA polymerase. From this study, (E)-5-(2-bromovinyl)-2'-deoxy-4'-thiouridine emerged as a promising candidate compound for the treatment of HSV-1 TK gene-transfected tumors in vivo, due to its metabolic stability (i.e., resistance to hydrolysis by thymidine phosphorylase).
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PMID:Comparative cytostatic activity of different antiherpetic drugs against herpes simplex virus thymidine kinase gene-transfected tumor cells. 802 17

Immunohistochemical detection of the nuclear antigen recognised by the monoclonal antibody Ki67, DNA polymerase alpha, and the proliferating cell nuclear antigen (PCNA), and histochemical staining for the argyrophilic proteins associated with the nucleolar organizer regions (AgNOR) were carried out on histological sections from 107 colorectal adenomas containing invasive carcinoma (ACIC), including 7 with regional lymph node metastases. Separate evaluations were made for fields corresponding to adenoma with low-grade dysplasia, adenoma with high-grade dysplasia and early cancer. The same techniques were also employed in 20 cases of normal mucosa and 20 advanced carcinomas. The mean percentages of Ki67, DNA polymerase alpha, and PCNA-positive nuclei and the number of AgNOR per nucleus progressively increased along the sequence from normal mucosa via low-grade and high-grade dysplasia adenoma to advanced cancer, whereas the early cancer values were not significantly different from those in the low-grade dysplasia areas. No significant difference in PCNA positivity and number of AgNOR were noted in ACIC with and without lymph node metastases. It is suggested that the decrease in proliferative activity thus revealed in early cancer may be due to changes in the submucosa microenvironment caused by invasion, and that the metastatic potential of an early colorectal cancer cannot be correlated to such activity.
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PMID:Cell proliferation in colorectal adenomas containing invasive carcinoma. 809 91

We studied cell kinetics of colo-rectal neoplasms using PCNA (the auxiliary protein of DNA polymerase-delta) immunohistochemistry. We analyzed the distribution pattern of PCNA positive cells on normal colon mucosa, adenoma (6 cases) and cancer (early: 33 cases, advanced: 6 cases). PCNA positive index (PI) was calculated as the percentage of PCNA positive tumor cells in relation to the total number (about 1000) of the tumor cells. PCNA positive indices were 30% in normal colon mucosa, 49% in adenoma and 72% in cancer, respectively. There were statistically significant differences between three mean values (p < 0.01). In normal colon mucosa PCNA positive cells are localized at the lower part of mucosa, but, in adenoma, they are found at the more upper part of mucosa too. In cancer, PCNA positive cells were localized diffusely and their immunoreactivity is higher than those of the normal mucosa and adenoma. In conclusion, our results suggests that the ratio of PCNA positive cells almost equivalents to growth fraction, and is correlated with the histological grading of colo-rectal tumor, but not correlated with depth of carcinoma. It is presumed that carcinoma has a higher ratio of PCNA positive cells than adenoma, and therefore carcinoma has higher proliferating cell density than adenoma.
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PMID:[A study of changes in distribution pattern of proliferating cells associated with progression of human colorectal benign and malignant tumor using PCNA immunohistochemistry]. 809 82

DNA polymerase alpha is a key enzyme in eukaryotic chromosomal DNA replication. tsFT20 is a temperature-sensitive mutant cell line derived from mouse mammary carcinoma FM3A cells, and the cells contain heat-labile DNA polymerase alpha and are arrested at the S phase at the nonpermissive temperature. We isolated cDNA of the catalytic subunit of DNA polymerase alpha from tsFT20 cells. DNA sequence analysis revealed that the cDNA from tsFT20 has a single mutation, a cytosine to thymine substitution that changes amino acid 1180 from serine to phenylalanine. We have also shown that tsFT20 cells could be rescued by transfection with the wild-type cDNA. These results demonstrate that the point mutation in the gene of DNA polymerase alpha causes the temperature-sensitive phenotype of tsFT20 cells and provide additional evidence that DNA polymerase alpha is essential for chromosomal replication in mammalian cells. We also detected mutation sites in one spontaneous and six N-methyl-N'-nitro-N-nitrosoguanidine-induced growth revertants of tsFT20 cells by single strand conformation polymorphism analyses and direct sequencing. All revertant cell lines had a second point mutation adjacent to the first mutation site in tsFT20 cells.
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PMID:Identification of a point mutation in the cDNA of the catalytic subunit of DNA polymerase alpha from a temperature-sensitive mouse FM3A cell line. 812 89

We have identified and purified a multiprotein form of DNA polymerase from the murine mammary carcinoma cell line (FM3A) using a series of centrifugation, polyethylene glycol precipitation, and ion-exchange chromatography steps. Proteins and enzymatic activities associated with this mouse cell multiprotein form of DNA polymerase include the DNA polymerases alpha and delta, DNA primase, proliferating cell nuclear antigen (PCNA), DNA ligase I, DNA helicase, and DNA topoisomerases I and II. The sedimentation coefficient of the multiprotein form of DNA polymerase is 17S, as determined by sucrose density gradient analysis. The integrity of the murine cell multiprotein form of DNA polymerase is maintained after treatment with detergents, salt, RNase, DNase, and after chromatography on DE52-cellulose, suggesting that the association of the proteins with one another is independent of nonspecific interaction with other cellular macromolecular components. Most importantly, we have demonstrated that this complex of proteins is fully competent to replicate polyomavirus DNA in vitro. This result implies that all of the cellular activities required for large T-antigen dependent in vitro polyomavirus DNA synthesis are present within the isolated 17S multiprotein form of the mouse cell DNA replication activities. A model is proposed to represent the mammalian Multiprotein DNA Replication Complex (MRC) based on the fractionation and chromatographic profiles of the individual proteins found to co-purify with the complex.
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PMID:A 17S multiprotein form of murine cell DNA polymerase mediates polyomavirus DNA replication in vitro. 812 85


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