Dados do Resumo

Título

Estrogen receptors regulate proteoglycans synthesis in castration-resistant prostate cancer

Introdução

Prostate cancer treatment includes androgen deprivation therapy. However, the disease can progress to an androgen-independent form, known as castration-resistant prostate cancer (CRPC). Proteoglycans (PGs) consist of a protein core to which glycosaminoglycan side chains are bound. These molecules can interact with proteins and growth factors and regulate cell’s behavior. Cellular and enzymatic alterations caused by cancer leads to an altered PGs structure and composition, modifying its function. Although studies have reported the correlation between estrogen receptors (ER) and PGs in breast cancer, its involvement in prostate cancer has not yet been elucidated.

Objetivo

The main purpose of this project is to analyze PGs expression and location in human cell lines that are CRPC models, after treatment with estrogen.

Métodos

DU-145 (derived from brain metastasis) and PC-3 (derived from bone metastasis) cell lines were cultured in RPMI 1640 Medium, without phenol red, with 10% fetal bovine serum, HEPES and gentamicin at 37°C, for 72 hours. Subsequently, culture medium was replaced to serum-free medium for 24 hours before assays. Real time PCR assays were performed to evaluate PGs expression (syndecans 1 and 4, versican and glypican-3) after treatment with 17β-estradiol (E2, 10 nM, for 24h). RNA was extracted using Trizol and Real time PCR was carried out using SYBR®-Green PCR Master Mix.

Resultados

DU-145 and PC-3 cell lines were treated at presence or absence of E2 (10nM) for 24 hours. RNA was extracted using Trizol and proteoglycans expression was assessed by Real time PCR. We observed an increase in syndecan-4 and versican proteoglycans expression at both cell lines after treatment with E2. For further confirmation, Western Blot assays will be carried out to evaluate these proteoglycans expression in DU-145 and PC-3 cell lines.

Conclusões

According to Real time PCR results, ERs activation after estrogen treatment leads to an increase of syndecan-4 (60% increase) and versican expression (80% increase). Previous studies have shown that versican controls cell migration and is expressed in prostate cancer stem cells. In turn, syndecan-4 is related to cancer cell adhesion and can form a complex with EGFR in breast cancer. Besides that, syndecan-4 is overexpressed in advanced prostate cancer. A further comprehension of the involvement of ER and PG in prostate cancer could contribute to a better understanding of the disease, as well as the discovery of new therapeutic targets.

Financiador do resumo

CAPES, FAPESP 2023/13622-1

Palavras Chave

Prostate cancer; Proteoglycans; Estrogen receptor