1.
Edsjö, Anders, et al.
(författare)
Differences in early and late responses between neurotrophin-stimulated trkA- and trkC-transfected SH-SY5Y neuroblastoma cells
2001
Ingår i: Cell Growth & Differentiation. - 1044-9523. ; 12:1, s. 39-50
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.
2.
Nilsson, Jonas, et al.
(författare)
Cloning, characterization and expression of human LIG1
2001
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 284:5, s. 1155-1161
Tidskriftsartikel (refereegranskat) abstract
Growth factor receptors are frequently amplified and over-expressed in various human cancers. Recently, a Drosophila cell surface protein, Kekkon-1, was found to participate in an epidermal growth factor (EGF) driven negative feedback loop. Kekkon-1 is induced by EGF, binds to the EGF-receptor, and inhibits receptor-mediated signaling. Here, we have searched for human genes with homologies to Kekkon-1 and identified human LIG1. The gene is the human homologue of mouse Lig-1 and is located on chromosome band 3p14, a region frequently deleted in various human cancers. It is predicted to encode a transmembrane cell-surface protein with extracellular leucine-rich repeats and immunoglobulin-like domains. LIG1 mRNA was detected in all tissues analyzed. The highest and lowest relative expression levels were found in brain and spleen, respectively, and differed by more than 200-fold. Taken together, our data are compatible with a role for LIG1 as a growth and tumor suppressor in human tissues.
3.
Ruuth, Kristina, et al.
(författare)
Interferon-alpha promotes survival of human primary B-lymphocytes via phoshatidylinositol 3-kinase
2001
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Academic Press. - 0006-291X .- 1090-2104. ; 284:3, s. 583-586
Tidskriftsartikel (refereegranskat) abstract
Signaling pathways for the antiviral and antiproliferative biological effects of type I interferons (IFN) are well established. In this report we demonstrate a novel signaling pathway for IFN-α, as it induced rapid phosphorylation of both PKB/Akt and its substrate forkhead. The PI3-kinase inhibitor LY294002 abolished these phosphorylations. PI3-kinase has been implicated in cell survival mediating its effect through the second messenger PIP3 and the subsequent activation of PKB/Akt. We could show that IFN-α inhibited spontaneous apoptosis of primary B-lymphocytes, in the absence of a mitogenic stimulus. This effect was inhibited by LY294002. Thus, our data suggests that IFN-α promotes survival of peripheral B-lymphocytes via the PI3-kinase-PKB/Akt pathway. In addition, IFN-α stimulation of anti-IgM activated cells resulted in downregulated expression of the cell cycle inhibitor p27/Kip1.
