To elucidate the possibility of utilizing protein kinase C (PKC) isoforms as target genes in neuroblastoma therapy, 5 neuroblastoma cell lines and neuroblastoma tumor specimens were examined for PKC isoform expression pattern and the cell lines were analyzed for sensitivity to PKC inhibition. All cell lines [IMR-32, LAN-2, LAN-5, SH-SY5Y and SK-N-BE(2)] expressed alpha, betaII, delta and epsilon isoforms of PKC, while no PKCeta or theta protein was detected in any cell line. PKCgamma was found only in LAN-2 cells. PKCalpha, betaII and delta were detected in 5 neuroblastoma tumors and PKCepsilon in 4 out of 5 tumors. Exposure to the PKC inhibitors GF109203X, Go 6976 or Go 6983 caused a decrease whereas activation of PKC with 12-O-tetradecanoyl phorbol 13-acetate caused an increase in the number of neuroblastoma cells. The effect of Go 6976 was due to both inhibited proliferation and to increased apoptosis. While GF109203X suppressed neurite outgrowth induced by a growth factor combination, Go 6976 potentiated neurite outgrowth. Our data suggest a role for classical PKC isoforms in neuroblastoma growth and survival and for novel isoforms in neurite outgrowth.
|Journal||International Journal of Cancer|
|Publication status||Published - 1999|
Bibliographical noteThe information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Molecular Medicine (013031200), Tumour Cell Biology (013017530), Division of Molecular Medicine and Gene Therapy (013022010)
Subject classification (UKÄ)
- Cancer and Oncology