Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The PRL gene is expressed at a high basal level in rat pituitary tumor GH3 cells, and this basal level enhancement of PRL gene expression is maintained through a Ca2+-calmodulin-dependent mechanism. We have now examined whether the enzyme, DNA topoisomerase II, which has been shown to be phosphorylated by a Ca2+-calmodulin-dependent protein kinase, plays a role in the Ca2+-calmodulin-dependent basal level enhancement of PRL gene expression. The topoisomerase II inhibitor, novobiocin, at concentrations in the range of 35-140 microM, effectively blocked the ability of Ca2+ to increase PRL mRNA levels. Examination of the effects of novobiocin on the levels of protein synthesis, glucose-regulated protein (GRP) 78 mRNA, histone 3 mRNA, and 18S ribosomal RNA indicated that the drug selectivity inhibited PRL gene expression. Two other topoisomerase II inhibitors, m-AMSA and VM26, also diminished the Ca2+-induced levels of PRL mRNA at concentrations (100-400 nM) that did not lower total mRNA levels. We then examined whether topoisomerase II interacted nonrandomly with DNA from the 5' transcribed and 5'-flanking region of the rat PRL gene by in vitro mapping of topoisomerase II DNA cleavage sites. In initial assays with a 10.5 kilobase (kb) PRL genomic DNA fragment containing 3.5 kb of 5'-transcribed DNA and 7 kb of 5'-flanking DNA, we detected 4 major cleavage sites in the following regions: site 1, +1500 to +1600; site 2, +1 to -100; site 3, -1200 to -1300; and site 4, -2900 to -3000.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for a role of topoisomerase II in the Ca2+-dependent basal level expression of the rat prolactin gene. 284 May 67

DNA topoisomerase IIalpha (Topo IIalpha) is a molecular and immunohistochemical marker that indicates proliferation rate and is the target for several antineoplastic agents. The present immunohistochemical study of a large series of surgically removed pituitary tumors was designed to assess the prognostic significance of Topo IIalpha expression relative to patient age, gender, tumor type and size, invasiveness, metastasis, MIB-1-labeling index and angiogenesis. Changes of Topo IIalpha expression in the tumors treated with bromocriptine and octreotide, a long-acting somatostatin analogue were also investigated. Topo IIalpha immunopositivity was detected only in the nuclei of tumor cells. Gonadotroph adenomas, null cell adenomas, and ACTH-producing adenomas had the lowest Topo IIalpha indices, whereas primary pituitary carcinomas and silent type 3 adenomas presented the highest counts. The statistical study demonstrated no significant correlation between Topo IIalpha expression, patient gender, and vascularity. In contrast, significant negative correlation was found between Topo IIalpha expression and patient age. Topo IIalpha expression was significantly higher in invasive than noninvasive tumors. A tendency to have higher counts was also observed in microadenomas compared with in macroadenomas. Although Topo IIalpha and MIB-1 indices were similar in most tumor types, no significant correlation between Topo IIalpha and MIB-1-labeling indices (r =.16, P =.09) was found. Only non-functioning adenomas showed positive correlation (r =.41, P =.006) between both proliferation markers. Our results demonstrated a significant decrease in Topo IIalpha index in octreotide-treated, GH-producing adenomas, compared with untreated tumors, but no significant changes were observed in bromocriptine-treated, PRL-producing adenomas. The present study showed no significant advantage of Topo IIalpha over MIB-1 as a prognostic marker; however, Topo IIalpha may provide crucial information regarding selection of adenohypophyseal tumors responsive to antineoplastic therapy, such as invasive pituitary adenomas and pituitary carcinomas, which exhibit a high Topo IIalpha index.
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PMID:Topoisomerase IIalpha expression in pituitary adenomas and carcinomas: relationship to tumor behavior. 1242

Pituitary adenomas represent an inhomogeneous tumor entity in terms of growth rate, invasiveness and recurrence. To improve understanding of their different biological behaviour, tumor cell proliferation markers are applied. The aim of this study was to assess proliferation rates overall and in clinico-pathological subgroups using MIB-1 and the recently introduced cell proliferation marker anti-topoisomerase-IIalpha (Topo-IIalpha). Further, we correlated the two markers, and defined the clinical value of Topo-IIalpha in pituitary adenomas as compared to MIB-1. We analyzed tumor cell proliferation rates using MIB-1 and Topo-IIalpha antibodies on samples of 260 primary pituitary adenomas. We excluded recurrent cases and cases with drug pretreatment. Median patient age at the time of surgery was 47 years (range 14-86 years), the male:female ratio was 1:1. The total cohort comprised 110 non-functioning and 150 functioning cases. Subtyping was performed according to hormonal expression as defined by WHO. Tumor size and invasiveness were noted from surgical and/or radio logical reports in 95% of cases. Overall MIB-1 index was median 1.8% (range 0.2-23.6%), Topo-IIalpha index was median 1.0% (range 0-14.4%) with a strong correlation between the two markers ( R=0.837, P<0.001). As compared to MIB-1, mean Topo-IIalpha values were significantly lower by a factor 1.8. Only MIB-1 was significantly higher in invasive as compared to non-invasive adenomas, in tumors < or =3 cm in diameter, and in the age-group 21-40. Female gender had significantly higher MIB-1 and Topo-IIalpha indices than male. Silent ACTH-cell and PRL-producing adenomas had the highest, null-cell adenomas and gonadotropinomas the lowest proliferation values, respectively. Our data show a strong correlation between MIB-1 and Topo-IIalpha indices in pituitary adenomas. Only MIB-1 but not Topo-IIalpha demonstrated significantly higher values in invasive adenomas. Therefore, MIB-1 seems more useful than Topo-IIalpha for decisions regarding postoperative patient management.
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PMID:Expression of cell proliferation markers in pituitary adenomas--correlation and clinical relevance of MIB-1 and anti-topoisomerase-IIalpha. 1525 5