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Protein Kinase C Is Required for Endothelin-1-Induced Proliferation of Human Myometrial Cells¹

^a INSERM U361, Université René Descartes, Pavillon Baudelocque, 75014 Paris, France

The role of protein kinase C (PKC)- in endothelin-1 (ET-1)-induced proliferation of human myometrial cells was investigated. Inhibition of conventional PKC with Gö 6976 eliminated the proliferative effect of ET-1. Treatment of myometrial cells with an antisense oligonucleotide against PKC efficiently reduced PKC protein expression without effect on other PKC isoforms and resulted in the loss of ET-1-induced cell growth. Immunocytochemistry using an antibody against PKC revealed that there was no PKC immunoreactivity in the nuclei of quiescent nonconfluent untreated cells, whereas it is evenly distributed throughout the cytoplasm. Exposure of myometrial cells to ET-1 for 15 min caused the PKC to shift towards the perinuclear area, and incubation for 60 min caused a shift towards the nucleus. These results reveal that PKC is required for ET-1-induced human myometrial cell growth and suggest that targeting of PKC by antisense nucleotides might be an important approach for the development of anticancer treatments.

First decision: 25 June 2001.

¹ This work was supported in part by grants from the Fondation pour la Recherche Médicale (FRM, France). We acknowledge Biognostik GmbH for their financial support.

² Correspondence: Michelle Breuiller-Fouché, INSERM U.361, Pavillon Baudelocque, 123, Bld de Port Royal, 75014 Paris, France. FAX: 33 1 43 26 44 08; breuiller-fouche{at}cochin.inserm.fr

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