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Expression and alterations of the PTEN / AKT / mTOR pathway in ameloblastomas
Author(s) -
Scheper MA,
Chaisuparat R,
Nikitakis NG,
Sauk JJ
Publication year - 2008
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/j.1601-0825.2007.01421.x
Subject(s) - pten , protein kinase b , pi3k/akt/mtor pathway , tensin , cancer research , p70 s6 kinase 1 , rptor , kinase , ribosomal s6 kinase , microbiology and biotechnology , biology , phosphorylation , signal transduction , chemistry
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.