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Título

LIPID PROFILE ASSOCIATED WITH SRC-3 AND CBP/P300 EXPRESSION IN CASTRATION-RESISTANT PROSTATE CANCER ANIMAL MODEL

Introdução, Material, Método, Resultados, Discussão e Conclusões

Introduction: CBP/p300 and SRC-3 genes are important for the control of metabolism and cellular energy homeostasis. In Prostate Cancer (PC), they are pointed as coactivators of the Androgen Receptor (AR), being possibly responsible for the castration resistance phenotype. The aim of the present study was to evaluate the expression levels of these genes associated with the lipid profile in hypercholesterolemic (HCOL) in vivo PC tumor model. Methods: The animals were divided into two groups, controls, receiving normal diet (N = 6) and animals receiving HCOL diet (N = 6). Animal serum lipids were measured by the LabTest. The xenograft tumor model was performed using PC3 cell line. Tumor volume was measured with a digital caliper rule. At the end of the experiment, tumors were resected, weighed and biochemical analyzes performed in the supernatant after maceration of tumor cells. Gene expression was determined by qRT-PCR. Results: Animals lipid profile showed higher total cholesterol and LDL levels in HCOL groups, p=0.037 and p=0.0001 respectively, being higher also in the tumor. Tumor volume (p=0.002) and tumor weight (p=0.001) were significantly higher in the HCOL. SRC-3 and CBP/p300 genes were overexpressed in the HCOL group, (p=0.021 and p=0.001) (Figure 1). Conclusion: The induction of HCOL diet was associated with higher weight and tumor volume, associated with higher expression levels of SRC-3 and CBP/p300 genes. We postulate that the increase in the lipid levels, result of a HCOL diet, may be associated with unfavorable behavior of castration resistance PC.

Palavras Chave

Prostate Cancer; CBP/p300; SRC-3; AR; CHOLESTEROL

Área

Câncer de Próstata Metastático

Instituições

Faculdade de Medicina da Universidade de São Paulo - Sao Paulo - Brasil

Autores

Ruan Pimenta, Juliana A Camargo, Nayara I Viana, Vanessa R Guimarães, Poliana R Silva, Guilherme L Gonçalves, Kátia R M Leite, William C Nahas, Miguel Srougi, Sabrina T Reis