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PI3K signaling inhibition in adenoid cystic carcinoma of salivary gland

Grant number: 13/08806-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2013
Effective date (End): July 31, 2014
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Yasmin Rodarte Carvalho
Grantee:Yonara Maria Freire Soares Marques
Home Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Estadual Paulista (UNESP). Campus de São José dos Campos. São José dos Campos , SP, Brazil

Abstract

The PI3K pathway controls the function of numerous substrates involved in regulation of cellular activities as cell growth, proliferation, survival and cell cycle progression. Many proteins take part of the PI3K signaling, however the main effector protein is Akt, which is of fundamental importance in cell proliferation and survival, but there are another proteins related with proliferation of this pathway, as mTOR. The Akt protein is downregulated by PTEN protein, which is an important tumor suppressor of this pathway and, frequently it is dysregulated in many cancers. The PI3K/Akt pathway is altered in many human cancers and it is widely studied in many glandular tumor as, breast and prostate carcinomas. In relation to salivary gland neoplasias, previous studies have been demonstrated dysregulation of PI3K signaling as, Akt overexpression and subcellular localization of PTEN. Furthermore, the hormonal influence have been reported as a possible initiator or promoter in carcinogeneses of adenoid cystic carcinoma of salivary gland. This hypothesis is based on findings of nuclear overexpression of ERbeta in ACC. In the present study we aim to investigate the isolated and combined with Tamoxifen response of PI3K inhibitor (LY29400 e Curcumin) in adenoid cystic carcinoma of salivary gland through in vivo and in vitro studies. The in vitro study are going to analyze protein related to PI3K pathway under treatment with PI3K inhibitor through western blotting and immunofluorecence assay; and the cytotoxity through anexina, MTT, trypan blue and cytometry assay. The in vivo study are going to analyze the expression of same proteins through immunohitochemical assay of tumors grew on animal model. (AU)