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

• Autorzy: Rubis B. , Grodecka-Gazdecka S. , Lecybyl R. , Ociepa M. , Krozowski Z. , Trzeciak W.H.
• Języki publikacji: EN

Abstrakty

EN

Contribution of the protein kinase A (PKA) and protein kinase C (PKC) signalling pathways to the regulation of 11y3-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, tetra- decanoyl 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 HSD11B2.

Słowa kluczowe

EN

gene expression; MCF-7 proliferation; signalling pathway; 11beta-hydroxysteroid dehydrogenase type 2; protein kinase C; protein kinase A; HSD11B2 gene

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2004
• Tom: 51
• Numer: 4
• Opis fizyczny: p.919-924,fig.,ref.

Twórcy

autor

Rubis B.

• University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland

autor

Grodecka-Gazdecka S.

autor

Lecybyl R.

autor

Ociepa M.

autor

Krozowski Z.

autor

Trzeciak W.H.

Bibliografia

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