Beta-catenin expression in human neural cell lines following exposure to cytokines and growth factors.
Beta-catenin acts as a key mediator of the Wnt/Wingless signaling pathway involved in cell proliferation, differentiation and survival. Recent studies have shown that an unstable interaction between beta-catenin and the mutant presenilin-1 induces neuronal apoptosis, and that beta-catenin levels are decreased in the brains of patients with Alzheimer's disease (AD). Since activated microglia and astrocytes play a role in the process of neuronal degeneration in AD, the cytokine/growth factor-regulated expression of beta-catenin in human neural cell lines, including NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N), IMR-32 neuroblastoma, SKN-SH neuroblastoma and U-373MG astrocytoma, was studied quantitatively following exposure to epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, transforming growth factor (TGF)-beta1, dibutyryl cyclic adenosine 3',5'-cyclic monophosphate (cAMP) (dbcAMP) or phorbol 12-myristate 13-acetate (PMA). Beta-catenin mRNA expressed constitutively in all of these cell lines was unaffected by treatment with any factors examined. In contrast, beta-catenin protein levels were reduced markedly in NTera2-N cells by exposure to dbcAMP, EGF or bFGF, and in U-373MG cells by treatment with dbcAMP or PMA, but were unaffected in any cell lines by BDNF, TNF-alpha, IL-1beta, IL-6, IFN-gamma or TGF-beta1. These results indicate that beta-catenin is expressed constitutively in human neural cells and downregulated at a protein level by a set of growth factors in a cell type-specific manner.
Department of Internal Medicine, Saga Medical School, Japan. satoj1@post.saga-med.ac.jp
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Satoh
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Kuroda
D001254:Astrocytoma; D001932:Brain Neoplasms; D003994:Bucladesine / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma; D006133:Growth Substances / Q000494:pharmacology*; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019572:Retinal Neoplasms; D012175:Retinoblastoma; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D016207:Cytokines; D003598:Cytoskeletal Proteins; D006133:Growth Substances; D015534:Trans-Activators; D051176:beta Catenin; D003994:Bucladesine; D013755:Tetradecanoylphorbol Acetate