Protein expression of PI3K/AKT/mTOR pathway in canine mast cell tumours

• Grant number: 13/04046-5
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: May 31, 2015
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Andrigo Barboza de Nardi
• Grantee: Andrigo Barboza de Nardi
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated researchers: Mirela Tinucci Costa ; Renee Laufer Amorim

Abstract

The PI3K/AKT/mTOR pathway is related to the proliferation, protein synthesis, survival and motility of the cells. It is described as the second most altered one in neoplastic processes, often associated with worse prognosis. The mast cell tumor (MT) is the most common skin cancer in dogs, and part of the molecular mechanisms involved in the pathogenesis of this tumor remain unknown. It is speculated that the activation of the PI3K/AKT/mTOR pathway may be related to the development of MT. So, this study aims to evaluate the protein expression of this pathway, through immunohistochemistry techinique, as this study has not been conducted on dogs with MT. Thirty patients from the Veterinary Oncology Service from UNESP, Campus Jaboticabal with histological diagnosis of MT will make part of it. These patients will be accompanied for one year after diagnosis and then divided in two groups according to the survival time, as described by Kiupel et al. (2011). The expression of p-AKT, p-mTOR, p-4EBP1, eIF4E and p-S6K1 will be evaluated in each group, these findings will be associated with the protein expression of Ki-67 and c-KIT, with the histological grade of the neoplasm, age, breed, presence of ulceration, size, location and the evolution time of the tumor, aiming to evaluate the prognostic potential of these proteins for canine MT. The evaluation of p-AKT and p-mTOR may also provide information about their predictive value, since currently specific inhibitors for AKT and mTOR in the treatment of various malignancies are already being used. (AU)