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

Alteration of the epidermal growth factor (EGF) signaling pathway occurs frequently in human cancer cells and may subsequently affect the cell survival towards anti-cancer agents. To elucidate the effect of long-term EGF treatment on the chemo-sensitivity of human cancer cells, human squamous carcinoma A431 cells (AP) were incubated continuously with 50 ng/ml EGF for 30 weeks and these cells were designated as the AC cells. The long-term EGF treatment did not alter the EGFR level and the EGF-induced protein tyrosine phosphorylation pattern in the AC cells. By MTT assay, the AC cells were shown to be more resistant than the AP cells to doxorubicin, etoposide and amsacrine but not to cisplatin. Among the drug-resistant proteins, topoisomerase IIalpha (topoII) was downregulated in the AC cells while there was no apparent change in the levels of P-glycoprotein, MRP-1 or glutathione- S-transferase-pi as compared to the AP cells. Furthermore, knockdown of topoII by antisense topoII oligonucleotide transfection decreased the sensitivity to doxorubicin, etoposide and amsacrine in the A431 cells. Results from the present study support an idea that long-term treatment with EGF may induce drug resistance in cells through the downregulation of topoII.
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PMID:Epidermal growth factor induction of resistance to topoisomerase II toxins in human squamous carcinoma A431 cells. 1696 95

Triple-negative breast carcinoma (TNBC) is one of the most aggressive subtypes of breast cancer and is associated with an unfavorable prognosis. The management of TNBC is currently based on the use of classical cytotoxic drugs, i.e., anthracyclines and/or microtubule-binding agents (TBAs). However, conventional chemotherapy is not always effective in these tumors and a systemic relapse is often observed, potentially due to the development of multi-drug resistance (MDR). Therefore, an improved understanding of MDR mechanisms may improve the therapeutic strategies for TNBC. In the present study, a paclitaxel-resistant (TxR) breast cancer cell subline of HCC1806 TNBC cells was established and characterized. The resistance index of this subline was calculated according to the IC50 of HCC1806-TxR relative to the parental HCC1806 cells (16.86-fold). TxR-cells also exhibited cross-resistance to vinblastin, doxorubicin and etoposide (~14-, ~4- and ~3-fold, respectively). As assessed with reverse transcription-quantitative polymerase chain reaction, TxR-resistant cells exhibited the upregulated expression of a number of multidrug resistance-associated genes, including MDR-1, MRP-1, -5, -6 and YB-1. The TxR cells also exhibited an increased expression of MDR-related proteins including MDR1 and MRP-1, which led to a substantial increase (5.4-fold) of the paclitaxel efflux from TxR-cells. In addition, the pro-apoptotic protein Fas was downregulated, whereas the anti-apoptotic Bcl-2 was upregulated, in TxR-cells. This may explain why a reduced extent of apoptosis was observed when TxR cells were exposed to TBAs and topoisomerase type II inhibitors, relative to the parental HCC1806 cells. Thus, the HCC1806-TxR cell line may serve as an appropriate model for the analysis of chemoresistance mechanisms in TNBCs, and for the investigation of novel anticancer agents for overcoming MDR-mediated mechanisms in TNBC.
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PMID:Establishment and characterization of a triple negative basal-like breast cancer cell line with multi-drug resistance. 2908 18