| Elevated level of nuclear protein kinase C in multidrug-resistant MCF-7 human breast carcinoma cells. | |
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MedLine Citation:
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PMID: 1617646 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies have demonstrated elevated levels of protein kinase C (PKC) activity in multidrug-resistant human breast carcinoma MCF-7/ADR cells compared to control drug-sensitive MCF-7/WT cells (R.L. Fine, J. Patel, and B.A. Chabner, Proc. Natl. Acad. Sci. USA, 85:582-586, 1988). In our present studies, immunohistochemical localization analysis using a polyclonal PKC antibody recognizing the alpha, beta, and gamma subtypes of PKC demonstrates that immunoreactivity is enhanced in MCF-7/ADR cells, with pronounced staining noted in the nuclear region. Other studies with purified nuclei isolated from MCF-7/ADR cells also show a marked increase in the intensity of immunostaining for PKC when compared to nuclei prepared from control MCF-7/WT cells. Western blot analysis of proteins extracted from purified nuclear preparations further establishes an increase in PKC enzyme protein associated with the nuclear fraction of MCF-7/ADR cells. Subcellular fractionation studies also indicate that MCF-7/ADR cells have 4-8 times higher nuclear PKC activity compared to that of control MCF-7/WT cells. MCF-7/ADR cells also possess 3-5-fold elevated cytosolic PKC activity, while a less than 2-fold increase is found in PKC activity associated with the plasma membrane fraction of MCF-7/ADR cells. Examination of these extracts with PKC isotype-specific antisera, as well as by DEAE-cellulose chromatography, reveals that nuclei prepared from MCF-7/ADR cells contain markedly elevated amounts of a slightly altered form of PKC alpha. These results suggest that elevated levels of a modified form of PKC alpha at the nucleus may play a role in modulating nuclear events to promote the development of multidrug resistance in MCF-7 cells. |
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Authors:
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S A Lee; J W Karaszkiewicz; W B Anderson |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cancer research Volume: 52 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1992 Jul |
Date Detail:
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Created Date: 1992-08-04 Completed Date: 1992-08-04 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 3750-9 Citation Subset: IM |
Affiliation:
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Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Blotting, Western Breast Neoplasms / enzymology*, pathology Cell Nucleus / enzymology* Chromatography, DEAE-Cellulose Doxorubicin / pharmacology Drug Resistance* Female Humans Immunohistochemistry Molecular Sequence Data Protein Kinase C / analysis* Tetradecanoylphorbol Acetate / pharmacology Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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16561-29-8/Tetradecanoylphorbol Acetate; 23214-92-8/Doxorubicin; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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