PMID- 18826385
OWN - NLM
STAT- MEDLINE
DCOM- 20090126
LR  - 20211203
IS  - 1601-0825 (Electronic)
IS  - 1354-523X (Linking)
VI  - 14
IP  - 6
DP  - 2008 Sep
TI  - Expression and alterations of the PTEN / AKT / mTOR pathway in ameloblastomas.
PG  - 561-8
LID - 10.1111/j.1601-0825.2007.01421.x [doi]
AB  - OBJECTIVES: Recently, an allelic loss of phosphatase and tensin homologue (PTEN) 
      was shown to occur in ameloblastomas. In carcinogenesis, loss of PTEN allows for 
      overactivity of the phosphatidylinositol-3-kinase/protein kinase B (PI3K / AKT) 
      pathway inducing an upregulation of mammalian-target of rapamycin (mTOR) and its 
      downstream effector ribosomal-subunit-6 kinase (S6K); allowing for uncontrolled 
      cell proliferation, apoptosis inhibition and cell cycle deregulation. METHODS: 
      Thirty ameloblastomas and five dental follicles were studied, looking at the 
      immunohistochemical expression of total PTEN and AKT, as well as their 
      phosphorylated (p) active forms, and the downstream effector and indicator of 
      mTOR activity p70 ribosomal-subunit-6 kinase (pS6K). Also assessed was the 
      expression of extracellular-signal-regulated kinase (ERK), which cross talks with 
      AKT. RESULTS: Total PTEN was absent in 33.3% of ameloblastomas, while its 
      stabilized, phosphorylated(ser380 / thr382 / thr383) form was absent in 83.3% of 
      tumors. In contrast, AKT was expressed in 83.3% of ameloblastomas, showing high 
      expression of the p-thr(308)AKT and p-ser(473) AKT forms in 93.3% and 56.6% of 
      cases, respectively. Further, the mTOR activated pS6K(ser240 / 244) was detected 
      in 86.7% of ameloblastomas, while ERK was overexpressed in 70.0% of the cases. 
      CONCLUSION: Immunohistochemical analysis of aberrant signaling in the 
      PI3K/AKT/mTOR pathway in ameloblastomas may represent a valuable tool for 
      elucidating pathogenesis, aggressiveness and selecting optimal therapeutics.
FAU - Scheper, M A
AU  - Scheper MA
AD  - Department of Diagnostic Sciences and Pathology, University of Maryland, 
      Baltimore, MD 21201, USA. mscheper@umaryland.edu
FAU - Chaisuparat, R
AU  - Chaisuparat R
FAU - Nikitakis, N G
AU  - Nikitakis NG
FAU - Sauk, J J
AU  - Sauk JJ
LA  - eng
PT  - Journal Article
PL  - Denmark
TA  - Oral Dis
JT  - Oral diseases
JID - 9508565
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 2)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Ameloblastoma/genetics/*pathology
MH  - Cell Proliferation
MH  - Dental Sac/pathology
MH  - Extracellular Signal-Regulated MAP Kinases/analysis
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Gingival Neoplasms/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Loss of Heterozygosity/genetics
MH  - Male
MH  - Mandibular Neoplasms/pathology
MH  - Maxillary Neoplasms/pathology
MH  - Middle Aged
MH  - PTEN Phosphohydrolase/*analysis
MH  - Phosphatidylinositol 3-Kinases/*analysis
MH  - Phosphorylation
MH  - Protein Kinases/*analysis
MH  - Proto-Oncogene Proteins c-akt/*analysis
MH  - Ribosomal Protein S6 Kinases, 70-kDa/analysis
MH  - TOR Serine-Threonine Kinases
MH  - Tooth, Impacted/pathology
MH  - Up-Regulation/genetics
MH  - Young Adult
EDAT- 2008/10/02 09:00
MHDA- 2009/01/27 09:00
CRDT- 2008/10/02 09:00
PHST- 2008/10/02 09:00 [pubmed]
PHST- 2009/01/27 09:00 [medline]
PHST- 2008/10/02 09:00 [entrez]
AID - ODI1421 [pii]
AID - 10.1111/j.1601-0825.2007.01421.x [doi]
PST - ppublish
SO  - Oral Dis. 2008 Sep;14(6):561-8. doi: 10.1111/j.1601-0825.2007.01421.x.