Novel and classical protein kinase C isoforms have different functions in proliferation, survival and differentiation of neuroblastoma cells

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Abstract
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 α, βII, δ and ϵ isoforms of PKC, while no PKCη or θ protein was detected in any cell line. PKCγ was found only in LAN‐2 cells. PKCα, βII and δ were detected in 5 neuroblastoma tumors and PKCϵ in 4 out of 5 tumors. Exposure to the PKC inhibitors GF109203X, Gö 6976 or Gö 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 Gö 6976 was due to both inhibited proliferation and to increased apoptosis. While GF109203X suppressed neurite outgrowth induced by a growth factor combination, Gö 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. Int. J. Cancer 81:494–501, 1999.