PTEN in Neural Precursor Cells: Regulation of Migration, Apoptosis, and Proliferation

Li, Li; Li, Fenghua; Salmonsen, Rebecca; Turner, Tod K.; Litofsky, N. Scott; Cristofano, Antonio Di; Pandolfi, Pier Paolo; Jones, Stephen N.; Recht, Larry; Ross, Alonzo H.

doi:10.1006/mcne.2002.1115

Cited by 116 publications

(96 citation statements)

References 49 publications

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“…Both PI3K and its negative regulator phosphatase and tensin homologue (PTEN) drive electrically regulated epithelial-cell migration and wound healing (Zhao et al, 2006) (see below). Emigration of neurons from the SVZ in rat is sensitive to PTEN, and mice lacking PTEN have several brain disorders including gliomas, macrocephaly and mental retardation; in each case, the lesion involves disrupted cell proliferation, cell migration and synaptogenesis (Li et al, 2002;Kwon et al, 2007). The discovery that EFs can control migration of neurons and neuronal stem cells as well as the extent of neuronal sprouting in vivo, and that these events might involve tumour suppressor genes, raises questions regarding the potential involvement of faulty extracellular electrical signalling in the genesis of neurodevelopmental diseases such as schizophrenia, autism, mental retardation and brain tumours (Box 3).…”

Section: Electrical Control Of Neuronal Migrationmentioning

confidence: 99%

Electrical dimensions in cell science

McCaig

Song

Rajnicek

2009

Journal of Cell Science

282

277

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Section: Electrical Control Of Neuronal Migrationmentioning

confidence: 99%

Electrical dimensions in cell science

McCaig

Song

Rajnicek

2009

Journal of Cell Science

282

277

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“…In vitro studies on Tsc1 −/− and Tsc2 −/− MEFs have demonstrated that this negative feedback mechanism blocks receptor tyrosine kinase-mediated activation of PI3K Harrington et al 2004;Shah et al 2004). Furthermore, heterozygous loss of Pten has been shown to be sufficient to activate Akt in the absence of receptor stimulation (DiCristofano et al 1999;Li et al 2002). Therefore, it seems likely that the TSC-related tumors that develop in the Tsc2 +/− Pten +/− mice are more severe due to reactivation of the many proliferation and survival pathways downstream of Akt, which are normally attenuated in absence of Tsc gene function.…”

Section: Genes and Development 1775mentioning

confidence: 99%

Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2

Manning¹,

et al. 2005

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The PTEN and TSC2 tumor suppressors inhibit mammalian target of rapamycin (mTOR) signaling and are defective in distinct hamartoma syndromes. Using mouse genetics, we find that Pten and Tsc2 act synergistically to suppress the severity of a subset of tumors specific to loss of each of these genes. Interestingly, we find that the slow-growing tumors specific to Tsc2 +/− mice exhibit defects in signaling downstream of Akt. However, Pten haploinsufficiency restores Akt signaling in these tumors and dramatically enhances their severity. This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature.Supplemental material is available at http://www.genesdev.org.

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“…Akt has been reported to alter the migration of several types of cells, including cortical neurons Li et al, 2002). For example, loss of PTEN increases Akt activity, and this is associated with an increase in migration (Li et al, 2002).…”

Section: Akt Expression Is Heterogeneous In Cortical Progenitorsmentioning

confidence: 99%

“…For example, loss of PTEN increases Akt activity, and this is associated with an increase in migration (Li et al, 2002). To assay effects of elevated Akt-1 expression on migration, we infected explants of E13.5 cortex with control or Akt virus and treated them with a combination of EGF and FGF2 for 3 d, which promotes migration out of explants.…”

Section: Akt Expression Is Heterogeneous In Cortical Progenitorsmentioning

confidence: 99%

Akt-1 Expression Level Regulates CNS Precursors

Sinor¹,

Lillien²

2004

J. Neurosci.

109

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Although most cells in the embryonic mouse cortex express the serine-threonine kinase Akt-1, a small population of progenitors expresses Akt-1 protein at a higher level. To determine the functional significance of this difference, we used a retrovirus to increase Akt-1 expression in cortical progenitors. Increased Akt expression enhanced Akt activation after growth factor stimulation of progenitors. In vivo, it promoted retention in progenitor layers, the ventricular zone and subventricular zone. In vitro, it enhanced proliferation and survival, but did not impair migration. Moreover, it increased the proportion of stem cells, defined by a self-renewal assay. These effects did not depend on the Akt substrate p21(Cip1). In contrast, rapamycin, an inhibitor of mTOR (mammalian target of rapamycin), altered effects of elevated Akt-1 selectively: it eliminated the increase in stem cells and reduced the proliferative response, but had no effect on survival. The ability of elevated Akt-1 to increase the self-renewing population therefore depends on a rapamycin-sensitive mechanism (presumably inhibition of mTOR activity) but not on p21(Cip1), and can be distinguished from its effects on the proliferation and survival of other types of progenitors. Our findings suggest that expression of a high level of Akt-1 by a subpopulation of cortical progenitors biases their responses to extrinsic signals to increase their survival, proliferation, and/or self-renewal. Heterogeneity in Akt-1 level among progenitors could therefore allow cells that share a microenvironment to respond differently to the same extrinsic signals.

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PTEN in Neural Precursor Cells: Regulation of Migration, Apoptosis, and Proliferation

Cited by 116 publications

References 49 publications

Electrical dimensions in cell science

Electrical dimensions in cell science

Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2

Akt-1 Expression Level Regulates CNS Precursors

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