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Título

Cholesterol induction increases levels of AR expression via positive regulation of its co-activators

Introdução, Material, Método, Resultados, Discussão e Conclusões

Introduction: SRC-1, SRC-2, SRC-3 are pointed as co-activators of the Androgen Receptor (AR) in Prostate Cancer (PC). These co-activators can promote the proliferation, survival, metabolism, activation, invasion and metastasis of cancer cells. The aim of the present study was to evaluate the role of cholesterol on the modulation of AR co-activators (SRC-1, 2 and 3) in a castration resistant prostate cancer (CRPC) cell line (PC3). Methods: The PC3 cell line was cultured and treated with cholesterol (2ug/mL - 8h). We performed the red oil test on cell culture to check for an increase in intracellular cholesterol. After RNA extraction, gene expression was determined by qRT-PCR. Results: An increase in intracellular cholesterol was observed in the PC3 cell line. The SRC-1 and SRC-3 co-activators showed higher levels of expression in the cholesterol-treated group (p = 0.028; p = 0.028 respectively). Although the SRC-2 gene showed greater expression in the group treated with cholesterol, it did not show statistical significance when compared to the control (p = 0.280). After the increase in co-activators, there was verify an increase in AR gene (p = 0.001). Conclusion: The
treatment of PC3 cells with cholesterol was associated with higher expression levels of SRC-1, SRC-2, SRC-3 and AR genes. We postulate that the increase in the cholesterol levels may be associated with unfavorable behavior of CRPC. Functional tests will be
carried out in the next cell assays to see if the increase in cholesterol may influence the potential for migration and increased proliferation (colony formation) in the PC3 cell line.

Palavras Chave

Prostate cancer, SRC-1, SRC-2, SRC-3, AR and cholesterol.

Área

Câncer de Próstata Metastático

Instituições

Faculdade de Medicina da USP - Sao Paulo - Brasil, Universidade Cidade de São Paulo - Sao Paulo - Brasil

Autores

Vitória Ghazarian Nunes, Nayara Izabel Viana, Vanessa Ribeiro Guimarães, Poliana Romão Silva, Gabriel Arantes Galvâo Dias dos Santos, Juliana Alves de Camargo, Katia Ramos Moreira Leite, Miguel Srougi, Ruan Pimenta, Sabrina Thalita dos Reis