PTEN in neural precursor cells: regulation of migration, apoptosis, and proliferation.
PTEN is a lipid phosphatase, and PTEN mutations are associated with gliomas, macrocephaly, and mental deficiencies. We have used PTEN +/- mice to assess PTEN's role in subventricular zone (SVZ) precursor cells. For cultured SVZ neurosphere cells, haploinsufficiency for PTEN increases phosphorylation of Akt and forkhead transcription factor and slightly enhances proliferation. Based on a filter penetration assay, PTEN +/- cells are substantially more migratory and invasive than +/+ cells. The +/- cells also are more resistant to H(2)O(2)-induced apoptosis. Analysis of PTEN +/- and +/+ mice by BrdU labeling reveals no difference in the rate of cell proliferation in the SVZ. Exit of BrdU-labeled cells from the SVZ and radial migration to the outer layers of the olfactory bulb are more rapid for +/- cells. These observations indicate that PTEN regulates SVZ precursor cell function and is particularly important for migration and apoptosis in response to oxidative stress.
Li
Li
L
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester 01605, USA.
Liu
Fenghua
F
Salmonsen
Rebecca A
RA
Turner
Tod K
TK
Litofsky
N Scott
NS
Di Cristofano
Antonio
A
Pandolfi
Pier Paolo
PP
Jones
Stephen N
SN
Recht
Larry D
LD
Ross
Alonzo H
AH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002452:Cell Count; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002552:Cerebral Ventricles / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051059:PTEN Phosphohydrolase; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics
D051858:Forkhead Transcription Factors; C486293:Foxf1 protein, mouse; D018129:Phosphatidylinositol Phosphates; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; D001973:Bromodeoxyuridine