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

To elucidate the possibility of utilizing protein kinase C (PKC) isoforms a s target genes in neuroblastoma therapy, 5 neuroblastoma cell lines and neu roblastoma tumor specimens were examined for PKC isoform expression pattern and the cell lines were analyzed for sensitivity to PKC inhibition. All ce ll lines [IMR-32, LAN-2, LAN-5, SH-SY5Y and SK-N-BE(2)] expressed alpha, be ta II, delta and epsilon isoforms of PKC, while no PKC eta or theta protein was detected in any cell line. PKC gamma was found only in LAN-2 cells, PK C alpha, beta II and delta were detected in 5 neuroblastoma tumors and PKC epsilon 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-tetra decanoyl phorbol 13-acetate caused an increase in the number of neuroblasto ma cells. The effect of Go 6976 was due to both inhibited proliferation and to increased apoptosis. While GF 109203X suppressed neurite outgrowth indu ced 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. (C) 1999 Wiley-Li ss, Inc.