Expression and alterations of the PTEN / AKT / mTOR pathway in ameloblastomas |
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Authors: | Scheper M A Chaisuparat R Nikitakis N G Sauk J J |
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Affiliation: | Department of Diagnostic Sciences and Pathology, University of Maryland, Baltimore, MD, USA;;Department of Oral Pathology and Oral Medicine, School of Dentistry, National and Kapodistrian University of Athens, Greece;;Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA |
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Abstract: | 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, phosphorylatedser380 / 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-thr308AKT and p-ser473 AKT forms in 93.3% and 56.6% of cases, respectively. Further, the mTOR activated pS6Kser240 / 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. |
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Keywords: | ameloblastoma dental follicle phosphatase and tensin homologue protein kinase B extracellular-signal-regulated kinase p70 ribosomal-subunit-6 kinase |
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