PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum.
PTEN is a tumour suppressor gene involved in cell cycle control, apoptosis and mediation of adhesion and migration signalling. Germline mutations of PTEN in humans are associated with familial tumour syndromes, among them Cowden disease. Glioblastomas, highly malignant glial tumours of the central nervous system frequently show loss of PTEN. Recent reports have outlined some aspects of PTEN function in central nervous system development. Using a conditional gene disruption approach, we inactivated Pten in mice early during embryogenesis locally in a region specific fashion and later during postnatal development in a cell-specific manner, to study the role of PTEN in differentiation, migration and neoplastic transformation. We show that PTEN is required for the realisation of normal cerebellar architecture, for regulation of cell and organ size, and for proper neuronal and glial migration. However, PTEN is not required for cell differentiation and lack of PTEN is not sufficient to induce neoplastic transformation of neuronal or glial cells
Marino
Silvia
S
Institute of Pathology, University Hospital, 8091 Zurich, Switzerland. silvia.marino@pty.usz.ch
Krimpenfort
Paul
P
Leung
Carly
C
van der Korput
Hetty A G M
HA
Trapman
Jan
J
Camenisch
Isabelle
I
Berns
Anton
A
Brandner
Sebastian
S
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000209:etiology*; D002531:Cerebellum / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018390:Gene Targeting; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human