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In vivo study of co-activators and co-repressors of androgen receptor in prostate cancer

Grant number: 19/00156-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2019
Effective date (End): May 31, 2022
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Sabrina Thalita dos Reis Faria
Grantee:Ruan César Aparecido Pimenta
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Prostate cancer (PCa) is characterized by slow growth and represents a type of androgen dependent neoplasia. The Androgen Receptor (AR) plays a key ro le in prostate carcinogenesis and metastasis. Thus, androgen deprivation therapies (ADT) are often used to treat PCa. However, at the time when PCa acquired castration-resistant phenotype (CPRC), ADT is no longer effective. In fact, it is now known that androgenic signaling persists even after the transition from the CaP hormone sensitive (HSPC) to CRPC. Among other factors that contribute to a clinical worsening of these patients are the lipid profiles, where it fits cholesterol, also known to be a common side effect ADT of for CRPC. In this sense, we emphasize the AR cofactors, which can recruit numerous transcriptional enzyme cofactors, such as p160 (SRC-1, SRC-2 and SRC-3), Histone Acetyltransferase (p300 and CBP), and corepressors, Cytoskeleton Protein (ARA67), Nuclear Receptor (SMRT / NCoR2) and IL-6. We also highlight the action of the microRNAs, 137 and 17-5p, which targets the p160 families and the CBP/p300 complex, respectively, which are also promising molecules in this sense. Thus, we believe that the joint study of these molecules in an in vivo model of hypercholesterolemic CPRC can elucidate the transactivation of the RA axis in this pathology, thus identifying possible biomarkers with potential therapeutic target.