Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the possible involvement of topoisomerases in embryonal differentiation, we examined the effect of topoisomerase inhibitors on the in vitro differentiation of mouse embryonal carcinoma F9 cells. We found that camptothecin, teniposide (VM-26), or genistein, specific inhibitors of topoisomerases, induced morphological as well as biochemical changes (production of tissue plasminogen activator, synthesis of laminin, and disappearance of stage-specific embryonic antigen 1) specific to F9 cell differentiation. Since these changes were indistinguishable from those observed in F9 differentiation induced by retinoic acid (plus dibutyryl cyclic AMP), it was suggested that inhibition of cellular topoisomerase activities triggered F9 cell differentiation into parietal endoderm-like cells in the same manner as retinoic acid (plus dibutyryl cyclic AMP). Experiments using differentiation-resistant mutant F9 cell lines, however, indicated that the molecular cascade involved in topoisomerase inhibitor-induced differentiation involves different steps from those functioning in the retinoic acid-induced differentiation cascade.
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PMID:Induction of in vitro differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases. 168 May 48

The Hox-2.1 gene is one of homeobox-containing genes located in the Hox-2 cluster on mouse chromosome 11. In this study, we have examined transcription of the Hox-2.1 gene during differentiation of F9 embryonal carcinoma cells induced by treatment with retinoic acid. The level of Hox-2.1 mRNA increases rapidly after induction of differentiation and then falls. Nuclear run-on experiments demonstrate that the rate of transcription for the Hox-2.1 gene also increases upon differentiation. Treatment of F9 cells with a DNA topoisomerase II inhibitor etoposide (VP-16) during differentiation blocks the accumulation of Hox-2.1 mRNA. Nuclear run-on analyses reveal that etoposide inhibits transcription of the Hox-2.1 gene during F9 cell differentiation. Measurements of the level of Hox-2.1 mRNA after blocking transcription by actinomycin D show that etoposide does not affect stability of the mRNA. These observations indicate that DNA topoisomerase II is involved in the control of Hox-2.1 gene transcription.
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PMID:Possible role of DNA topoisomerase II on transcription of the homeobox gene Hox-2.1 in F9 embryonal carcinoma cells. 168 82

A small number of testicular germ cell tumours are refractory to current chemotherapy regimens. DNA topoisomerase I is the target for several new drugs and a potential candidate treatment for chemorefractory germ cell tumours. DNA topoisomerase II alpha is the target for etoposide, which is currently used regularly in germ cell tumour treatment. The expression of DNA topoisomerase I and II alpha were therefore assessed immunohistochemically in a range of testicular tumours, especially those with persistent malignant elements on retroperitoneal lymph node dissection. Pre-chemotherapy orchidectomy specimens were matched with post-chemotherapy retroperitoneal lymph node dissections to examine changes in expression. There was considerable variation in the expression of topoisomerase I in different tumour types. Both yolk sac tumours and teratoma, mature showed universal expression of topoisomerase I, while 38% of seminomas and 30% of embryonal carcinomas were positive. Strong topoisomerase II alpha expression was found in embryonal carcinoma. There was a negative correlation between topoisomerase I and II alpha expression (P=0.004) and downregulation of topoisomerase II alpha after chemotherapy (P=0.02). Topoisomerase I expression appears to increase in those cases with residual teratoma, mature, but is largely unchanged in those cases remaining as embryonal carcinoma. These results suggest that topoisomerase I inhibitors may be useful in chemorefractory germ cell tumours, especially yolk sac tumours and where there are unresectable residual teratoma, mature deposits.
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PMID:DNA topoisomerase I and II expression in drug resistant germ cell tumours. 1223 72