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

• Authors: Błażej Rubiś , Sylwia Grodecka-Gazdecka , Remigiusz Lecybył , Marta Ociepa , Zygmunt Krozowski , Wiesław H Trzeciak
• Languages of publication: 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.

Keywords

EN

MCF-7 proliferation; HSD11B2 gene expression; 11β-hydroxysteroid dehydrogenase type II; signalling pathways

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2004
• Volume: 51
• Issue: 4
• Pages: 919-924

Dates

published

2004

received

2004-05-25

revised

2004-10-08

accepted

2004-10-11

Contributors

author

Błażej Rubiś

• Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland

author

Sylwia Grodecka-Gazdecka

• Department of Oncology, University of Medical Sciences, Poznań, Poland

author

Remigiusz Lecybył

• Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland

author

Marta Ociepa

• Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland

author

Zygmunt Krozowski

• Baker Heart Research Institute, Molecular Hypertension Laboratory, Melbourne, Australia

author

Wiesław H Trzeciak

• Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland

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