Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been widely used as a control RNA in Northern blotting and in reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. We investigated the expression of GAPDH in a large series of primary breast cancers and in MCF7 human mammary epithelial breast cancer cells treated with oestradiol. The expression of GAPDH was quantified by a real-time one-step RT-PCR assay, based upon the 5' nuclease activity of Taq polymerase using an Abi Prism 7700 Sequence Detector System (Perkin Elmer, France). Using the Spearman test, GAPDH expression was found to correlate inversely with the age of the patients at diagnosis (P = 0.003; r = -0.147), oestradiol receptors (ER) (P<0.0001; r = -0.327) and progesterone receptors (PgR) (P < 0.0001; r = -0.206). A positive correlation was observed between GAPDH expression and the histo-prognostic grading (HPG) (P < 0.0001; r = 0.344). Moreover, the overall survival (OS) and the relapse-free survival (RFS) were significantly reduced in patients whose tumours showed an enhanced level of GAPDH expression (OS, P = 0.046; RFS, P = 0.021). Multivariate analyses demonstrated that GAPDH was not an independent prognostic factor. Finally, in MCF7 cells treated with oestradiol. a statistically significant dose-dependent increase in GAPDH expression was observed. These results show that GAPDH expression is associated with breast cancer cell proliferation and with the aggressiveness of tumours. The present study demonstrates that, in cancer, the use of GAPDH gene expression should not be used as a control RNA.
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PMID:Glyceraldehyde-3-phosphate dehydrogenase gene expression in human breast cancer. 1088 9

Given that transposons are so abundant in mammalian genomes, it is natural to assume that through their maintenance the host gains some net benefit. This need not be true; sexual reproduction allows a transposon to go to fixation if the reduction in fitness of the host is anything less than two-fold. Obligate outcrossing sexual reproduction therefore favors the evolution of aggressive transposons, which in turn select for the evolution of host mechanisms that suppress transposon activity. Hosts that have asexual or self-fertilizing generations will select for transposons that are more benign and self-limiting than those of obligate sexuals, and obligate asexuals and uniparental organelle genomes will be free of active transposons if these impose any fitness penalty. We are interested in host mechanisms that suppress transposons in sexuals and have found that mammals (all of which are obligate sexuals) control their large populations of potentially active retroposons by methylating the five position of cytosine residues within promoter elements. This causes strong transcriptional repression and assembly of the affected sequences into the condensed state. Methylation also causes permanent inactivation in the germline by driving C-->T transition mutations at methylated sites. It is now known that methylation remains in place for the large majority of the life of germ cells and is essential for control of the very large transposon burden. There is pressure on transposons to evolve mechanisms that overcome host suppression, and over evolutionary time, the balance swings back and forth between parasite and host. The ability of the mammalian genome to absorb and accumulate additional transposons has caused the amount of reverse transcriptase coding sequence in the human genome to far exceed the sum total of all cellular coding sequence. While transposons could, in principle, contribute functions useful to the host, the fact that asexual species and uniparental organelle genomes lack transposons is strong evidence that transposons have a net deleterious effect even in genomes that might be thought to require an additional source of plasticity. The abundance of transposons in many genomes cannot be taken as evidence of a mutualistic relationship, and the conflict between transposons and genomes may have actually retarded rather than accelerated evolution. It is suggested that the relationship between sex and transposons is as follows: (i) Obligate sexuals will tend to harbor aggressive transposons limited largely by host suppressive mechanisms, which in mammals involve methylation of transposon promoters. (ii) The aggressiveness of transposons in facultative sexuals and self-fertilizing sexuals will be in part self-limited and will be proportional to the relative frequency of asexual and outcrossing sexual generations. (iii) Obligate asexuals arid organelles transmitted in a uniparental manner will have no active transposons if these have a net negative effect on host fitness.
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PMID:Sex brings transposons and genomes into conflict. 1095 19

The presence of circulating tumor cells in bone marrow and peripheral blood of cancer patients may reflect the aggressiveness of the disease. This also applies to cancers that rarely give rise to overt bone marrow metastases. The clinical validity of micrometastasis detection for staging and prognostication depends on the sensitivity and reliability of the detection method. In malignant melanoma, most studies have used reverse transcriptase polymerase chain reaction (RT-PCR) techniques, commonly with tyrosinase mRNA as the target molecule. Unfortunately, highly inconsistent results have been reported, raising doubts about this approach. In a study of 81 melanoma patients with metastatic disease, we used an immunobead rosetting method in which live melanoma cells are selected and identified by binding of paramagnetic beads coated with the 9.2.27 antibody against the high molecular weight melanoma-associated antigen. In bone marrow samples obtained from 60 patients, 14 (23.3%) were positive, compared to only two of 81 in blood. A highly significant correlation (p = 0.0001, log rank test) was found between micrometastasis positivity and overall survival from time of removal of the primary tumor. Moreover, in regression analysis it was found that the presence of micrometastatic cells was an independent and the most important indicator of poor prognosis, with a relative risk of 5.38. The immunomagnetic method is simple, rapid, and highly sensitive and will be used in further prospective clinical studies.
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PMID:Immunobead-based detection and characterization of circulating tumor cells in melanoma patients. 1109 32

We measured the expression of the type I growth factor receptor gene family [epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4] in a series of 365 unselected primary breast cancers. The expression was quantified with a real-time one-step reverse transcriptase-PCR (RT-PCR) assay, based upon the 5' nuclease activity of the Taq polymerase and using an Abi Prism 7700 Sequence Detector System (Perkin-Elmer, Courtaboeuf, France). c-erbB-3 and c-erbB-4 were positively correlated to each other (Spearman test) and negatively correlated to EGFR. EGFR and c-erbB-2 were inversely correlated to the presence of estradiol receptors (ER) and progesterone receptors (PgR), and positively correlated to the histoprognostic grading (HPG). Conversely, c-erbB-3 and c-erbB-4 were positively correlated to the presence of ER and PgR, and inversely correlated to the grading HPG. EGFR was inversely related (chi2 test) to the presence of ER and PgR, and positively associated with HPG. In contrast, both c-erbB-3 and c-erbB-4 were inversely related to HPG, and positively associated with the presence of ER and PgR. The expression level of EGFR and c-erbB-2 was significantly higher in ER- and PgR-negative tumors compared with ER- and PgR-positive tumors (Student's t test), and in tumors with higher grade compared with tumors with lower grade. The expression level of c-erbB-3 and c-erbB-4 was significantly higher in ER- and PgR-positive tumors compared with ER- and PgR-negative tumors and in tumors with lower grade compared with tumors with higher grade. In overall survival studies, Cox univariate analyses showed prognostic values of EGFR [> or = median; P = 0.026; risk ratio (RR), 1.6], c-erbB-3 (> or = median; P = 0.0093; RR, 0.58), c-erbB-4 (> or = median; P = 0.0024; RR, 0.52), HPG, node involvement, tumor diameter, ER, and PgR. In Cox multivariate analyses, tumor diameter, ER, and PgR had a prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of tumor diameter, node involvement, and c-erbB-4 (P = 0.015; RR, 0.65). These three parameters maintained their prognostic value in multivariate analyses (c-erbB-4, P = 0.035; RR, 0.67). This study confirms that EGFR expression and c-erbB-2 expression are markers of tumor aggressiveness in breast cancer. Conversely, we demonstrate that c-erbB-3 and c-erbB-4 elevated expressions are associated with a better prognosis.
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PMID:Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. 1110 35

Loss of heterozygosity (LOH) on the long arm of chromosome 13 is common in human breast tumors, pointing to the existence of several suppressor genes in this region. LOH at 13q14 has been implicated in alterations of retinoblastoma gene (RB1) expression. However, attempts to identify a link between the absence of retinoblastoma protein expression and LOH at the RB1 locus by means of immunohistochemical techniques have produced conflicting results. Therefore, we quantified RB1 mRNA by means of reverse transcriptase-polymerase chain reaction in a large series of human sporadic primary breast tumors. RB1 gene underexpression was observed in 28 (21.7%) of 129 breast-tumor RNAs. Allelic loss at this locus correlated with RB1 mRNA underexpression (P < 10(-7)), demonstrating a causal link. These data, based on a technique other than immunohistochemistry, confirm that RB1 is the main target of the 13q14 LOH observed in human breast cancer. We also found that RB1 underexpression correlated with Scarff-Bloom-Richardson (SBR) histopathologic grade III (P = 0.033), negative estrogen-receptor status (P = 0.026) and large tumor size (P = 0.010). The latter correlation was due mainly to a high mitotic index (one of the three components comprising SBR grade), suggesting that RB1 influences the proliferation rate of breast tumors. RB1 status (underexpression vs. normal expression) was not associated with subsequent relapse or with shorter relapse-free survival. This study shows a major role of the RB1 gene in the pathogenesis of breast cancer. RB1 gene underexpression promotes breast-tumor aggressiveness and rapid tumor-cell proliferation, making RB1 an outstanding target for future gene-based breast-cancer therapy.
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PMID:Loss of heterozygosity at 13q14 correlates with RB1 gene underexpression in human breast cancer. 1110 60

To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and systematically analyzed the expression pattern of the human NK/T cell line (NK-YS) genome by cDNA expression array and tissue microarray. We detected significant changes in the gene expression of NK-YS cell line: an increase in 18 and a decrease in 20 genes compared to normal NK cells or peripheral blood mononuclear cells. Among these genes, we found a strong decrease in hematopoietic cell specific protein-tyrosine-phosphatase SH-PTP1 (SHP1) mRNA by cDNA expression array and reverse transcriptase-polymerase chain reaction. Further analysis with standard immunohistochemistry and tissue microarray, which used 207 paraffin-embedded specimens of various kinds of malignant lymphomas, showed that 100% of NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma were negative for SHP1 protein expression. On the other hand, SHP1 protein was strongly expressed in the mantle zone and interfollicular zone lymphocytes in reactive lymphoid hyperplasia specimens. In addition, various kinds of hematopoietic cell lines, particularly the highly aggressive lymphoma/leukemia lines, lacked SHP1 expression in vitro, suggesting that loss of SHP1 expression may be related to not only malignant transformation, but also tumor cell aggressiveness. SHP1 expression could not be induced in either of two NK/T cell lines by phorbol ester, suggesting that genetic impairment or modification with methylation of SHP1 DNA could be one of the critical events in the pathogenesis of NK/T lymphoma. This evidence strongly suggests that loss of SHP1 gene expression plays an important role in multistep tumorigenesis, possibly as an anti-oncogene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.
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PMID:Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray. 1158 76

Clinical and histopathological evaluations are inadequate for assessing biological aggressiveness and regrowth potential in benign pituitary adenomas. To develop reliable and prognostically informative means of predicting behavior remains an intractable problem. Telomerase, a reverse transcriptase that extends telomere length, may facilitate tumorigenesis and tumor immortality. In the present study, we investigated the telomerase activity of pituitary adenomas, and attempted to assess the value of telomerase expression for predicting their clinical course. In total, 31 (30 patients) benign pituitary adenoma samples including 8 recurrent adenomas were studied. Telomerase expression was evaluated by polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay and telomerase activity levels were quantitated by improved PCR enzyme-linked immunosorbent assay (ELISA). The data were analyzed in relation to clinical course which was reviewed at 4-5.5 years (median follow-up time, 52.5 months) after surgery. The relative values of the telomerase expression for predicting the clinical course were compared with the MIB-1 antigen-based proliferative cell index (PCI) and p53 immunoreactivity which have recently been suggested to correlate with aggressive behavior in pituitary adenomas. Overall, telomerase expression was detected in 13% of the adenomas (4 tumor tissues, 3 patients). These adenomas comprised large, invasive, and functioning adenomas. The number of telomerase-positive adenomas was small; however, the PCI was higher in cases with telomerase expression (4 tumor tissues; mean, 4.2 +/- 2.4%) than in those without it (27 tumor tissues; 1.4 +/- 1.3%) (p = 0.01). One tumor with detectable telomerase expression, which did not undergo additional pharmacological or radiotherapeutic intervention after first surgery, recurred rapidly despite gross total surgical resection, although the PCI of both the primary and recurrent adenomas was not high. Detection of telomerase expression may represent an additional useful means of identifying aggressive behavior, complementing the histopathological evaluation of benign-appearing pituitary adenomas.
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PMID:Telomerase activity in pituitary adenomas: significance of telomerase expression in predicting pituitary adenoma recurrence. 1282 19

The PEA3/E1AF/ETV4 gene encodes an Ets-related transcription factor that is expressed in the epithelial cells of the mammary gland. Previous reports have shown that PEA3 can up-regulate promoter activities of many genes associated with tumorigenesis. A significant fraction of those encode matrix metalloproteinases (MMP genes) required for degradation of the extracellular matrix. To better obtain a molecular characterization of PEA3 expression in sporadic breast cancer, we quantified PEA3 mRNA by means of real-time reverse transcriptase-polymerase chain reaction assay in a large series of human primary breast tumors. PEA3 expression showed wide variations in tumor tissues, being under-expressed in 30 of 130 (23.1%) and over-expressed in 18 of 130 (13.8%) compared with normal breast tissues. High PEA3 mRNA levels correlated significantly with Scarff-Bloom-Richardson histopathological grade III (P = 0.018) but not with poor prognosis, suggesting that PEA3 is a marker of tumor aggressiveness rather than a prognostic factor in human breast cancer. We also observed positive links between the expression of PEA3 and those of MKI67 and ERBB2 (P = 0.034 and P = 0.045, respectively) and an inverse relationship with ERalpha (P = 0.0016). Our results do not support recent findings suggesting that PEA3 could be a tumor-suppressor gene that can act therapeutically in ERBB2 over-expressed tumors. Our results also suggest major roles of the MMP2, NRG1 and CGB genes (which encode type I gelatinase, heregulin and human chorionic gonadotropin beta subunit, respectively) in the PEA3 pathway dysregulation observed in breast cancer. Taken together, the data confirm the role of the PEA3 gene in breast tumorigenesis, and suggest the existence of numerous other still unknown genes transactivated by the PEA3 transcription factor.
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PMID:Expression of PEA3/E1AF/ETV4, an Ets-related transcription factor, in breast tumors: positive links to MMP2, NRG1 and CGB expression. 1463 60

Interleukin-7 (IL-7), a haematopoietic growth factor, is known to induce the differentiation and proliferation of some haematological malignancies including certain types of leukaemias and lymphomas. However, little is known about its role in solid tumours, including breast cancer. In this study, the expression level of IL-7, IL-7 receptor (IL-7R) and their downstream signalling molecules, including the Janus kinases (Jak-1 and Jak-3), phosphoinositide 3-kinase (PI3-K) and signal transducers and activators of transcription (Stat-5) were analysed using the reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR and immunohistochemistry in a cohort of patients with breast cancer. The results were analysed in relation to tumour grade, TNM stage, patients' prognosis (using the Nottingham Prognostic Index (NPI)) and survival. The levels of expression of IL-7, IL-7R, Jak-1, Jak-3, PI3-K and Stat-5 were significantly higher in the most aggressive tumours. With the exception of Stat-5 expression, the transcript copies of IL-7 and all other signalling molecules were higher in patients with the worst prognoses (NPI3) and in patients who died from breast cancer after 72 months of follow-up. This aberrant expression of IL-7 and its signalling intermediates in invasive breast cancers could have significant diagnostic and prognostic implications. Measuring these molecules in breast cancer tissues may provide, for the first time, important molecular indicators of tumour differentiation, aggressiveness, nodal status, prognosis and patient survival.
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PMID:Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human breast cancer. 1496 14

Alterations in the control of cell cycle progression have been implicated in a wide variety of malignant neoplasms, including prostate cancer. CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. CDC25C plays an important role in the G2-M transition by activating Cdc2/Cyclin B1 complexes. To determine whether CDC25C activity is altered in prostate cancer, we have examined the expression of CDC25C and an alternatively spliced variant in human prostate cancer samples and cell lines. CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form. Expression of a biologically active alternatively spliced CDC25C isoform is also increased in prostate cancer and expression of alternatively spliced CDC25C is correlated to occurrence of biochemical (prostate-specific antigen) recurrence. We have also developed a quantitative reverse transcriptase-PCR analysis of Ki-67 expression as a method of measuring proliferative activity in prostate cancer from RNA samples. Based on this analysis of Ki67 expression, some but not all of this increase in CDC25C and its alternatively spliced variants is correlated with increased proliferation in prostate cancer. This data suggests that CDC25C might play an important role in prostate cancer progression and could be used to monitor and predict the aggressiveness of this disease.
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PMID:Increased expression and activity of CDC25C phosphatase and an alternatively spliced variant in prostate cancer. 1600 May 64


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