PAkt, cyclin D1 and p27/Kip.1 in glioblastomas with and without EGFR amplification and PTEN mutation.
BACKGROUND
PIP3, generated by P13-K activates Akt which inactivates AFX/FKHR; with the consequent decrease in p27/Kip.1 expression and enhancement of cyclin D1 expression through FRAP/mTOR. PTEN lipid phosphatase degrades PIP3 and negatively regulates Akt, whereas this is activated by EGFR through PI3. In glioblastomas, PTEN is mutated in 27%-40% and EGFR amplified in 60%-65% of cases.


METHODS
PTEN mutation and EGFR amplification by PCRP Akt, p27/Kip.1 and cyclin D1 by immunohistochemistry, apoptosis by TUNEL and MIB.1 LI were studied in a series of 65 operated glioblastomas.


RESULTS
EGFR amplification and PTEN mutation were present in 50% and 30% of glioblastomas, respectively. No relationship between EGFR amplification and PTEN mutation, and p27/Kip. 1 and cyclin D1 was found. However, cyclin D1 was positive in 69% of Akt-expressing areas, whereas p27 was positive in 30% only.


CONCLUSIONS
A direct relationship is more evident between cyclin D1 and p27/Kip.1 and Akt than with PTEN and EGFR.
Fiano
Valentina
V
Department of Neuroscience, University of Turin, Via Cherasco, 15 and Turin, Italy.
Ghimenti
Chiara
C
Imarisio
Sara
S
Silengo
Lorenzo
L
Schiffer
Davide
D
D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D016543:Central Nervous System Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005784:Gene Amplification; D018773:Genes, erbB-1 / Q000235:genetics*; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics*
D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human