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Interplay between the fibronectin and prostate cancer: analysis of genes and microRNAs involved in the STAT3 pathway

Grant number: 14/25702-0
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2015
Effective date (End): February 28, 2017
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Flávia Karina Delella
Grantee:Bruno Martinucci
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The extracellular environment is a complex network comprising of the extracellular matrix (ECM) and regulatory molecules. The ECM has a primary role in regulating numerous cellular events such as adhesion, proliferation, differentiation, and others. A fine balance between synthesis and turnover determines the ultimate composition of the ECM, and when deregulated can lead to the development of tissue damage and cancer. Prostate cancer (PCa) is one of the cancers with higher mortality among men in the world. In the prostate, the interactions between the epithelial tissue and the surrounding stroma are responsible for maintaining the physiological function through proliferative and migratory restrictions. In cancer, many cells lose these restrictions, while the abnormal ECM deregulate behavior of stromal cells lead to generation of a tumorigenic microenvironment. Recent findings indicate that human tumors have unregulated expression of microRNAs, molecules considered new oncogenes or tumor suppressors that can regulate ECM components, and these may be regulated by ECM components. Thus, considering the importance of integrity in the interaction between epithelial and extracellular components for maintaining the prostate homeostasis and that this pattern is lost during carcinogenesis progression is expected to determine and correlate the role of MEC in important miRNAs in CaP. For this, prostate tumor cells (LNCaP) and immortalized normal prostate cells (RWPE-1) will be exposed to fibronectin in 2D and 3D culture model, and will be, subsequently performed expression analysis, by RT-qPCR technique, of miRNAs 21, 125b and 145 involved in the STAT3 pathway, and of its target gene (STAT3, c-Myc, PTEN). Furthermore, will be performed the quantification and localization of the proteins, Bcl-2, N-cadherin, E-cadherin, MMP-2 and MMP-9 by Western blotting and immunohistochemistry techniques, respectively. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARTINUCCI, BRUNO; MINATEL, BRENDA DE CARVALHO; CUCIELO, MAIRA SMANIOTTO; MEDEIROS, MARIANA; VECHETTI-JUNIOR, IVAN JOSE; FELISBINO, SERGIO LUIS; DELELLA, FLAVIA KARINA. Basement membrane extract attenuates the more malignant gene expression profile accentuated by fibronectin in prostate cancer cells. Molecular and Cellular Biochemistry, v. 451, n. 1-2, p. 131-138, JAN 2019. Web of Science Citations: 0.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MARTINUCCI, Bruno. Relação entre a fibronectina e o câncer de próstata análise de genes e microRNAs. 2017. Master's Dissertation - Universidade Estadual Paulista "Júlio de Mesquita Filho" Instituto de Biociências (Campus de Botucatu)..

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