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- Edsjö, Anders, et al.
(författare)
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Differences in early and late responses between neurotrophin-stimulated trkA- and trkC-transfected SH-SY5Y neuroblastoma cells
- 2001
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Ingår i: Cell Growth & Differentiation. - 1044-9523. ; 12:1, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- Despite their sympathetic neuroblast origin, highly malignant neuroblastoma tumors and derived cell lines have no or low expression of the neurotrophin receptor genes, trkA and trkC. Expression of exogenous trkA in neuroblastoma cells restores their ability to differentiate in response to nerve growth factor (NGF). Here we show that stable expression of trkC in SH-SY5Y neuroblastoma cells resulted in morphological and biochemical differentiation upon treatment with neurotrophin-3 (NT-3). To some extent, trkA- and trkC-transfected SH-SY5Y (SH-SY5Y/trkA and SH-SY5Y/trkC) cells resembled one another in terms of early signaling events and neuronal marker gene expression, but important differences were observed. Although induced Erk 1/2 and Akt/PKB phosphorylation was stronger in NT-3-stimulated SH-Y5Y/trkC cells, activation of the immediate-early genes tested was more prominent in NGF-treated SH-SY5Y/ trkA cells. In particular, c-fos was not induced in the SH-SY5Y/trkC cells. There were also phenotypic differences. The concentrations of norepinephrine, the major sympathetic neurotransmitter, and growth cone-located synaptophysin, a neurosecretory granule protein, were increased in NGF-treated SH-SY5Y/trkA but not in NT-3-treated SH-SY5Y/trkC cells. Our data suggest that NT-3/p145trkC and NGF/p140trkA signaling differ in some aspects in neuroblasoma cells, and that this may explain the phenotypic differences seen in the long-term neurotrophin-treated cells.
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| 4. |
- Zeidman, Ruth, et al.
(författare)
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Novel and classical protein kinase C isoforms have different functions in proliferation, survival and differentiation of neuroblastoma cells
- 1999
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Ingår i: International Journal of Cancer. - 0020-7136. ; 81:3, s. 494-501
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Tidskriftsartikel (refereegranskat)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 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.
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