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Keratoacanthoma of the Lip: Activation of the mTOR Pathway, Tumor Suppressor Proteins, and Tumor Senescence.

Abstract
The PI3K-PTEN-mTOR is one of the most important pathways involved in cancer development and progression; however, its role in keratoacanthoma (KA) is poorly understood. In this study, we investigated the activation of key proteins in the PI3K-mTOR pathway in lip KA. We analyzed the activation of the PI3K-PTEN-mTOR pathway using human tumor samples stained for well-established protein markers in this pathway, including pS6 and pAKT phosphoproteins. We assessed proliferation using Ki-67 and performed additional morphological and immunohistochemical analysis using anti-PTEN and anti-p16 antibodies.We found that the majority of KA labeled to pS6 and not pAKT. PTEN expression was inversely correlated with Ki-67 expression. In addition to PTEN expression, KA cells were positive for p16 senescence marker. PI3K-PTEN-mTOR pathway is activated in lip KA, leading to downstream activation of mTORC1, but not mTORC2. This pathway plays an important role in KA progression by promoting proliferation and activation of oncogenic-induced senescence.
AuthorsCaroline Siviero Dillenburg, Manoela Domingues Martins, Luise Meurer, Rogerio Moraes Castilho, Cristiane Helena Squarize
JournalMedicine (Medicine (Baltimore)) Vol. 94 Issue 38 Pg. e1552 (Sep 2015) ISSN: 1536-5964 [Electronic] United States
PMID26402814 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
Chemical References
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Phosphatidylinositol 3-Kinase
  • PTEN protein, human
  • PTEN Phosphohydrolase
Topics
  • Aged
  • Cell Aging (physiology)
  • Female
  • Humans
  • Immunohistochemistry
  • Keratoacanthoma (metabolism, pathology)
  • Lip Neoplasms (metabolism, pathology)
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase (metabolism)
  • Phosphatidylinositol 3-Kinase (metabolism)
  • Signal Transduction
  • TOR Serine-Threonine Kinases (metabolism)

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