A significant proportion of breast cancers with HER2 amplification show simultaneous amplification or deletion of Topo 2. Amplification of Topo 2 may lead to the overexpression of the Topo 2 protein and ultimately to hypersensitivity to Topo 2 inhibitors. HER2 and Topo 2 gene status in breast cancer patients has been determined in several studies using immunohistochemistry, florescence in situ ...

OBJECTIVE To investigate the effects of β-Elemene (β-ELE) on the proliferation, apoptosis, and topoisomerase I (TOPO I) and topoisomerase IIα (TOPO IIα) expression and activity of human hepatocarcinoma HepG-2 cells. METHODS After treatment with β-ELE, morphological alterations of HepG-2 cells were observed under an inverted microscope. Cell proliferation was assessed using an MTT assay, cell ...

Studies were conducted to determine the possible involvement of DNA topoisomerase II (Topo II) in the induction of differentiation in two human promyelocytic HL-60 leukemia cell variants that are either susceptible or resistant to differentiation induced by phorbol-12-myristate-13-acetate (PMA), a protein kinase C activator. The acquisition of maturation markers and changes in the activity, lev...

Modulators of the DNA unwinding enzyme, topoisomerase I (Topo I), inhibit DNA repair and augment the lethal effects of X-rays and other agents that create breaks in DNA. To investigate the role of Topo I in DNA repair, we examined Topo I activity before and after X-irradiation using confluence-arrested hamster and human cells. Topo I activities were higher in unirradiated neoplastic compared to...

Murine transgenic cell lines lacking DNA topoisomerase II (topo II)b have been used to assess the importance of topo IIb as a drug target. Western blot analysis confirmed that the topo IIb 2/2 cell lines did not contain topo IIb protein. In addition, both the topo IIb 1/1 and topo IIb 2/2 cell lines contained similar levels of topo IIa protein. The trapped in agarose DNA immunostaining assay (T...

DNA topoisomerase II (topo II) is thought to be a nuclear enzyme; during interphase most was insoluble and could be recovered in the pellet after centrifugation of cell homogenates at 10,000 g (P-10). Upon entry into mitosis, the majority of topo II did not associate with condensed chromosomes but was apparently solubilized and redistributed throughout the cell. Although two non-chromosomal sub...

Type II DNA topoisomerases (Topo II) are essential enzymes implicated in key nuclear processes. The recent discovery of a novel kind of Topo II (DNA topoisomerase VI) in Archaea led to a division of these enzymes into two non-homologous families, (Topo IIA and Topo IIB) and to the identification of the eukaryotic protein that initiates meiotic recombination, Spo11. In the present report, we hav...

DNA damage is attended by rapid recruitment of endogenous type I topoisomerase (topo I) into covalent cleavage complexes with genomic DNA in vivo. In contrast, endogenous topoisomerase II alpha and beta are not stimulated by DNA damage. We show that topo I and p53 are able to associate at arrested topo I-genomic DNA covalent complexes in vivo, suggesting that p53 directly stimulates topo I acti...

BACKGROUND Biomarkers may help to improve non-small cell lung cancer (NSCLC) prognosis. However, the prognostic effect of topoisomerase I (Topo I) on NSCLC is unknown. We evaluated the clinicopathologic and prognostic significance of tumor Topo I and thymidylate synthase (TS) protein expression in postoperative NSCLC patients. METHODS One hundred and fifteen patients with postoperative NSCLC ...

Most DNA topoisomerase II (topo II) in cell-free extracts of 0-2-h old Drosophila embryos appears to be nonnuclear and remains in the supernatant after low-speed centrifugation (10,000 g). Virtually all of this apparently soluble topo II is particulate with a sedimentation coefficient of 67 S. Similar topo II-containing particles were detected in Drosophila Kc tissue culture cells, 16-19-h old ...