Abstract:
:We have investigated the role of protein kinase C (PKC) in the multidrug resistance (MDR) phenotype of human KB carcinoma cell lines. The PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) reduced daunomycin accumulation in both drug-sensitive KB-3-1 and MDR KB-C1 cells in a time-dependent manner. The inactive phorbol ester 4 alpha TPA did not reduce daunomycin accumulation, and the PKC inhibitor, Ro 31-8220, reversed the TPA effect. TPA had no effect on daunomycin efflux and did not induce Pgp expression in KB-3-1 cells or alter Pgp levels in KB-C1 cells. Linear, short-term daunomycin accumulation was reduced by pretreatment with TPA, an effect that could be reversed by Ro 31-8220. The effects of TPA on PKC subspecies localisation and downregulation were also examined. TPA initially induced translocation of PKCs alpha and delta, and to a lesser extent, PKC epsilon to the membrane fraction; 8 h after TPA treatment, differential effects on downregulation of PKCs alpha and delta were observed between cell lines, although PKC epsilon was not reduced in either cell line. We therefore propose that the TPA-induced reduction in daunomycin accumulation in KB cells is due to a PKC-mediated process, which is maintained after depletion of certain PKC subspecies or is due to activation of downregulation insensitive PKC subspecies. These results suggest that PKC may regulate drug resistance by reducing drug influx in a Pgp-independent manner in KB cells. This may represent a mechanism of drug-resistance independent of, or in addition, to, Pgp-mediated drug efflux.
journal_name
Oncol Resjournal_title
Oncology researchauthors
Drew L,Groome N,Warr JR,Rumsby MGsubject
Has Abstractpub_date
1996-01-01 00:00:00pages
249-57issue
6eissn
0965-0407issn
1555-3906journal_volume
8pub_type
杂志文章abstract::Human papillomavirus type 16 (HPV16) is a major causative factor in the development of uterine cervical carcinomas. We investigated the role of E6/E7 in tumor formation. Skin-specific E6/E7 transgenic mice showed approximately twice as many tumors compared with nontransgenic mice in dimethylbenz[a]anthracene (DMBA)-in...
journal_title:Oncology research
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doi:10.3727/000000006783980964
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journal_title:Oncology research
pub_type: 杂志文章
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journal_title:Oncology research
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doi:10.3727/096504017X15051723858706
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journal_title:Oncology research
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journal_title:Oncology research
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doi:10.3727/096504016X14761384026719
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journal_title:Oncology research
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journal_title:Oncology research
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更新日期:1998-01-01 00:00:00
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journal_title:Oncology research
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更新日期:2011-01-01 00:00:00
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journal_title:Oncology research
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::MicroRNAs (miRNAs) are emerging as pivotal regulators in the development and progression of various cancers, including renal cell carcinoma (RCC). MicroRNA-384 (miR-384) has been found to be an important cancer-related miRNA in several types of cancers. However, the role of miR-384 in RCC remains unclear. In this stud...
journal_title:Oncology research
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doi:10.3727/096504017X15035025554553
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doi:10.3727/096504018X15188747585738
更新日期:2018-10-17 00:00:00
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journal_title:Oncology research
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journal_title:Oncology research
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
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journal_title:Oncology research
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doi:10.3727/096504011x13079697132790
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journal_title:Oncology research
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journal_title:Oncology research
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journal_title:Oncology research
pub_type: 杂志文章
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journal_title:Oncology research
pub_type: 杂志文章,评审
doi:
更新日期:1997-01-01 00:00:00
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journal_title:Oncology research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Oncology research
pub_type: 杂志文章
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更新日期:2000-01-01 00:00:00
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journal_title:Oncology research
pub_type: 杂志文章
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更新日期:2018-08-23 00:00:00