Protein kinase Cα is required for endothelin-1-induced proliferation of human myometrial cells

The role of protein kinase C (PKC)-alpha in endothelin-1 (ET-1)induced proliferation of human myometrial cells was investigated. Inhibition of conventional PKC with Go 6976 eliminated the proliferative effect of ET-1. Treatment of myometrial cells with an antisense oligonucleotide against PKC alpha efficiently reduced PKC alpha 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 alpha revealed that there was no PKC alpha 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 alpha to shift towards the perinuclear area, and incubation for 60 min caused a shift towards the nucleus. These results reveal that PKC alpha is required for ET-1-induced human myometrial cell growth and suggest that targeting of PKC alpha by antisense nucleotides might be an important approach for the development of anticancer treatments.