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Relationship of LRP-human major vault protein toin vitro and clinical resistance to anticancer drugs
Miguel A. Izquierdo George L. Scheffer Marcel J. Flens Robert H. Shoemaker Leonard H. Rome Rik J. Scheper 《Cytotechnology》1996,19(3):191-197
Multidrug resistance (MDR) has been related to two members of the ABC-superfamily of transporters, P-glycoprotein (Pgp) and Multidrug Resistance-associated Protein (MRP). We have described a 110 kD protein termed the Lung Resistance-related Protein (LRP) that is overexpressed in several non-Pgp MDR cell lines of different histogenetic origin. Reversal of MDR parallels a decrease in LRP expression. In a panel of 61 cancer cell lines which have not been subjected to laboratory drug selection, LRP was a superior predictor forin vitro resistance to MDR-related drugs when compared to Pgp and MRP, and LRP's predictive value extended to MDR unrelated drugs, such as platinum compounds. LRP is widely distributed in clinical cancer specimens, but the frequency of LRP expression inversely correlates with the known chemosensitivity of different tumour types. Furthermore, LRP expression at diagnosis has been shown to be a strong and independent prognostic factor for response to chemotherapy and outcome in acute myeloid leukemia and ovarian carcinoma (platinum-based treatment) patients. Recently, LRP has been identified as the human major protein. Vaults are novel cellular organelles broadly distributed and highly conserved among diverse eukaryotic cells, suggesting that they play a role in fundamental cell processes. Vaults localise to nuclear pore complexes and may be the central plug of the nuclear pore complexes. Vaults structure and localisation support a transport function for this particle which could involve a variety of substrates. Vaults may therefore play a role in drug resistance by regulating the nucleocytoplasmic transport of drugs.Abbreviations LRP
Lung Resistance-related Protein
- MVP
Major Vault Protein
- MDR
Multidrug resistance
- MRP
Multidrug resistance-associated Protein
- NPC
Nuclear Pore Complex
- Pgp
P-glycoprotein 相似文献
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Involvement of nuclear transcription factor Sp1 in regulating glucose transporter-1 gene expression during rat trophoblast differentiation. 总被引:3,自引:0,他引:3
Y Okamoto M Sakata T Yamamoto Y Nishio K Adachi K Ogura M Yamaguchi T Takeda K Tasaka Y Murata 《Biochemical and biophysical research communications》2001,288(4):940-948
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H Kusaba M Nakayama T Harada M Nomoto K Kohno M Kuwano M Wada 《European journal of biochemistry》1999,262(3):924-932
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植物中,UDP-L-鼠李糖是细胞壁骨架的主要成分,由鼠李糖合成酶催化底物UDP-α<,-D->葡萄糖合成.本实验从拟南芥基因组中分离了鼠李糖合成酶基因AtRHM1 1058bp的启动子序列并对启动子5'端进行了不同长度的缺失.将全长启动子及不同缺失启动子与GUS报告基因进行融合后转化野生型拟南芥,获得了一系列转基因植株.启动子缺失分析结果表明,AtRHM1基因在转录水平上受葡萄糖的诱导,参与葡萄糖应答反应的顺式调控元件位于启动子的-931 bp~-752bp区域. 相似文献
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