Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo
- PMID: 15520182
- DOI: 10.1158/0008-5472.CAN-04-2487
Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo
Abstract
Somatic mutations of PTEN are found in many types of cancers including glioblastoma, the most malignant astrocytic tumor. PTEN mutation occurs in 25 to 40% of glioblastomas but is rarely observed in low-grade glial neoplasms. To determine the role of Pten in astrocytes and glial tumor formation, we inactivated Pten by a Cre-loxP approach with a GFAP-cre transgenic mouse that induced Cre-mediated recombination in astrocytes. Pten conditional knockout mice showed a striking progressive enlargement of the entire brain. Increased nuclear and soma size was observed in both astrocytes and neurons, which contributed in part to the increase in brain size. Pten-deficient astrocytes showed accelerated proliferation in vitro and aberrant ongoing proliferation in adult brains in vivo. In contrast, neurons lacking Pten did not show alterations in proliferation. This study shows cell-type dependent effects of Pten loss in the adult brain, including increased astrocyte proliferation that may render astroglial cells susceptible to neoplastic transformation or malignant progression.
Similar articles
-
Somatic induction of Pten loss in a preclinical astrocytoma model reveals major roles in disease progression and avenues for target discovery and validation.Cancer Res. 2005 Jun 15;65(12):5172-80. doi: 10.1158/0008-5472.CAN-04-3902. Cancer Res. 2005. PMID: 15958561
-
mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo.Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12923-8. doi: 10.1073/pnas.2132711100. Epub 2003 Oct 8. Proc Natl Acad Sci U S A. 2003. PMID: 14534328 Free PMC article.
-
Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease.Nat Genet. 2001 Dec;29(4):404-11. doi: 10.1038/ng781. Nat Genet. 2001. PMID: 11726927
-
PTEN and myotubularin: novel phosphoinositide phosphatases.Annu Rev Biochem. 2001;70:247-79. doi: 10.1146/annurev.biochem.70.1.247. Annu Rev Biochem. 2001. PMID: 11395408 Review.
-
Pten signaling in gliomas.Neuro Oncol. 2002 Jul;4(3):196-211. Neuro Oncol. 2002. PMID: 12084351 Free PMC article. Review.
Cited by
-
Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma.Front Pharmacol. 2019 Nov 7;10:1316. doi: 10.3389/fphar.2019.01316. eCollection 2019. Front Pharmacol. 2019. PMID: 31787897 Free PMC article.
-
Multifaceted Regulation of PTEN Subcellular Distributions and Biological Functions.Cancers (Basel). 2019 Aug 26;11(9):1247. doi: 10.3390/cancers11091247. Cancers (Basel). 2019. PMID: 31454965 Free PMC article. Review.
-
Decrease in PTEN and increase in Akt expression and neuron size in aged rat spinal cord.Exp Gerontol. 2010 Jun;45(6):457-63. doi: 10.1016/j.exger.2010.03.015. Epub 2010 Mar 27. Exp Gerontol. 2010. PMID: 20347952 Free PMC article.
-
Combinatorial tissue engineering partially restores function after spinal cord injury.J Tissue Eng Regen Med. 2019 May;13(5):857-873. doi: 10.1002/term.2840. Epub 2019 Mar 20. J Tissue Eng Regen Med. 2019. PMID: 30808065 Free PMC article.
-
Roscovitine, a Cyclin-Dependent Kinase-5 Inhibitor, Decreases Phosphorylated Tau Formation and Death of Retinal Ganglion Cells of Rats after Optic Nerve Crush.Int J Mol Sci. 2021 Jul 28;22(15):8096. doi: 10.3390/ijms22158096. Int J Mol Sci. 2021. PMID: 34360858 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous
