ArticleProceedings of the National Academy of Sciences of the United States of America2004
Inhibition of neuronal phenotype by PTEN in PC12 cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 68 citations in OpenAlex.
- Review
- Nerve Growth Factor Induces Proliferation and Aggressiveness In Prostate Cancer Cells.Cancers · 2019Article
- Beyond Trophic Factors: Exploiting the Intrinsic Regenerative Properties of Adult Neurons.Frontiers in cellular neuroscience · 2019Review
- PTEN-GSK3β-MOB1 axis controls neurite outgrowth in vitro and in vivo.Cellular and molecular life sciences : CMLS · 2018Article
- NaCell death discovery · 2018Article
- PTEN Promotes Dopaminergic Neuronal Differentiation Through Regulation of ERK-Dependent Inhibition of S6K Signaling in Human Neural Stem Cells.Stem cells translational medicine · 2016Article
- Central Neurocytoma: A Review of Clinical Management and Histopathologic Features.Brain tumor research and treatment · 2016Review
- The Protective Role of microRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress.Frontiers in molecular neuroscience · 2016Article
- Measuring PI3K Activation: Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer.Molecular cancer research : MCR · 2015Article
- Association of p75(NTR) and α9β1 integrin modulates NGF-dependent cellular responses.Cellular signalling · 2015Article
- Involvement of the Na+/Ca2+ exchanger isoform 1 (NCX1) in neuronal growth factor (NGF)-induced neuronal differentiation through Ca2+-dependent Akt phosphorylation.The Journal of biological chemistry · 2015Article
- Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits.Molecular autism · 2015Article
- Brain patterning perturbations following PTEN loss.Frontiers in molecular neuroscience · 2014Review
- Phosphatidylinositol 4-phosphate 5-kinase α negatively regulates nerve growth factor-induced neurite outgrowth in PC12 cells.Experimental & molecular medicine · 2013Article
- Regulation of axonal growth and neuromuscular junction formation by neuronal phosphatase and tensin homologue signaling.Molecular biology of the cell · 2012Article
- Protein phosphatase magnesium dependent 1A (PPM1A) plays a role in the differentiation and survival processes of nerve cells.PloS one · 2012Article
- Isoform diversity and regulation in peripheral and central neurons revealed through RNA-Seq.PloS one · 2012Article
- A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development.Development (Cambridge, England) · 2011Article
- The influence of electric fields on hippocampal neural progenitor cells.Stem cell reviews and reports · 2010Article
- Morphine induces ubiquitin-proteasome activity and glutamate transporter degradation.The Journal of biological chemistry · 2008Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms of neuronal differentiation in PC12 cells are still not completely understood. Here, we report that the tumor suppressor PTEN has a profound effect on differentiation by affecting several pathways involved in nerve growth factor (NGF) signaling. When overexpressed in PC12 cells, PTEN (phosphatase and tensin homologue deleted on chromosome ten) blocked neurite outgrowth induced by NGF. In addition, these cells failed to demonstrate the transient mitogenic response to NGF, as well as subsequent growth arrest. Consistent with these observations was a finding that PTEN significantly inhibits NGF-mediated activation of the members of mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways, crucial for these processes. While exploring possible mechanisms of PTEN effects on NGF signaling, we discovered a significant down-regulation of both high-affinity (TrkA) and low-affinity (p75) NGF receptors in PTEN-overexpressing clones. Subsequent microarray analysis of several independent clonal isolates revealed a myriad of neuronal genes to be affected by PTEN. All of these changes were validated by quantitative PCR. Of particular interest were the genes for the key enzymes of the dopamine synthesis pathway, receptors for different neurotransmitters, and neuron-specific cytoskeleton proteins, among others. Some, but not all effects could be reproduced by pharmacological inhibitors of PI3K and/or MAPK, suggesting that PTEN may influence some genes by mechanisms independent of these signaling pathways. Our findings may shed new light on the role of this tumor suppressor during normal brain development and suggest a previously uncharacterized mechanism of PTEN action in neuron-like cells.
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