Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypoxia-inducible factor (HIF) 1alpha is a key regulator of the cellular response to oxygen deprivation. Specific disruption of the HIF-1 pathway is important for exploring its role in tumor biology and developing more efficient weapons to treat cancer. In this study, we stably transfected human breast tumor MCF-7 cells with short hairpin RNA expression vectors targeting HIF-1alpha. After knockdown of HIF-1alpha, hypoxia-induced expression of its target genes such as vascular endothelial growth factor, Glut-1, phosphoglycerate kinase, and P-glycoprotein were markedly attenuated. Moreover, HIF-1alpha knockdown was found to suppress the shift from S-phase to G(1) induced by hypoxia and increase drug sensitivity to methotrexate. The growth rates of HIF1alpha-knockdown tumors were drastically retarded in both subcutaneous and orthotopic xenograft models, which were accompanied by decreased angiogenesis and reduced expression of glucose transporter in tissue sections. These data demonstrate that HIF-1alpha knockdown reduces tumorigenicity of MCF-7 cells and suggest a promising combination of both anti-HIF-1 strategy and traditional chemotherapy to improve cancer treatment.
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PMID:Knockdown of hypoxia-inducible factor-1alpha in breast carcinoma MCF-7 cells results in reduced tumor growth and increased sensitivity to methotrexate. 1651 53

Chemoresistance is a poor prognostic factor in breast cancer and, thus, presents a significant clinical challenge. The mechanisms of chemoresistance involve multiple complex biological processes. This study aims to identify common contributory factors to chemoresistance in breast cancer by comparing protein expression profiles of chemosensitive MCF-7 breast cancer cells and cells resistant to two different commonly used anti-cancer drugs (adriamycin and paclitaxel). Expression of the ATP binding cassette transporter, P-glycoprotein (P-gp), in breast tumours has previously been found to correlate with poor prognosis in vivo and, accordingly, we confirmed overexpression of P-gp in both adriamycin- and paclitaxel-resistant MCF-7 cells. Using two-dimensional gel electrophoresis and MALDI-TOF peptide mass fingerprinting, we identified 20 proteins differentially expressed between chemosensitive, adriamycin-resistant and paclitaxel-resistant MCF-7 cells. Cytokeratin-8, keratin-19, Hsp-27, 14-3-3 epsilon, annexin-A2 and phosphoglycerate kinase-1 showed altered expression in both adriamycin- and paclitaxel-resistant cells. Validation of a number of these changes was confirmed by Western blotting. Our findings provide further insights into the complex mechanisms of chemoresistance, as well as representing an attractive starting point for the identification of potential protein biomarkers to predict response to chemotherapy in breast cancer in vivo.
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PMID:Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs. 1748 77