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2004 | 51 | 4 | 919-924
Article title

Contribution of protein kinase A and protein kinase C signalling pathways to the regulation of HSD11B2 expression and proliferation of MCF-7 cells.

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EN
Abstracts
EN
Contribution of the protein kinase A (PKA) and protein kinase C (PKC) signalling pathways to the regulation of 11β-hydroxysteroid dehydrogenase type II (HSD11B2) gene expression was investigated in human breast cancer cell line MCF-7. Treatment of the cells with an adenylyl cyclase activator, forskolin, known to stimulate the PKA pathway, resulted in an increase in HSD11B2 mRNA content. Semi-quantitative RT-PCR revealed attenuation of the effect of forskolin by phorbol ester, tetradecanoyl phorbol acetate (TPA), an activator of the PKC pathway. It was also demonstrated that specific inhibitors significantly reduced the effect of activators of the two pathways. Stimulation of the PKA pathway did not affect, whereas stimulation of the PKC pathway significantly reduced MCF-7 cell proliferation in a time-dependent manner. A cell growth inhibitor, dexamethasone, at high concentrations, caused a 40% decrease in proliferation of MCF-7 cells and this effect was abolished under conditions of increased HSD11B2 expression. It was concluded that in MCF-7 cells, stimulation of the PKA signal transduction pathway results in the induction of HSD11B2 expression and that this effect is markedly reduced by activation of the PKC pathway. Activation of the PKC pathway also resulted in inhibition of cell proliferation, while activation of the PKA pathway abolished the antiproliferative effect of dexamethasone. These effects might be due to oxidation of dexamethasone by the PKA-inducible HSD11B2g.
Publisher

Year
Volume
51
Issue
4
Pages
919-924
Physical description
Dates
published
2004
received
2004-05-25
revised
2004-10-08
accepted
2004-10-11
Contributors
  • Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland
  • Department of Oncology, University of Medical Sciences, Poznań, Poland
  • Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland
author
  • Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland
  • Baker Heart Research Institute, Molecular Hypertension Laboratory, Melbourne, Australia
  • Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland
References
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Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv51i4p919kz
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