Document Detail


Elevated level of nuclear protein kinase C in multidrug-resistant MCF-7 human breast carcinoma cells.
MedLine Citation:
PMID:  1617646     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S A Lee; J W Karaszkiewicz; W B Anderson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer research     Volume:  52     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1992 Jul 
Date Detail:
Created Date:  1992-08-04     Completed Date:  1992-08-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3750-9     Citation Subset:  IM    
Affiliation:
Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
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MeSH Terms
Descriptor/Qualifier:
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:
16561-29-8/Tetradecanoylphorbol Acetate; 23214-92-8/Doxorubicin; EC 2.7.11.13/Protein Kinase C

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