Correlation between estrogen receptor ESR1-36 (ER¿-36) and EGFR in PC-3 and DU-145 androgen-independent prostate cancer cells

• Grant number: 24/17065-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Carolina Meloni Vicente
• Grantee: Camila Rebelo Morgado Costa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Initially, prostate cancer depends on androgen to evolve, but it can gradually progress to an androgen-independent form of the disease, also known as castration-resistant prostate cancer (CRPC). The molecular mechanisms involved in this stage of the disease are not fully understood and the current therapies are insufficient to improve the survival of patients. Previous studies from our laboratory have shown that, in androgen-independent prostate cancer cells (PC-3 and DU-145), the estrogen receptors ESR1 (ER¿) and ESR2 (ER¿) are mostly located outside the nucleus of these cells, indicating the activation of rapid signaling pathways. Estrogen receptor isoforms ESR1-36 have been detected in different types of tumors, but in prostate cancer, their function needs to be explored. Signaling crosstalk of ESR1-36 (ER¿36) and EGFR (Epidermal Growth Factor Receptor) in breast and endometrium tumors have been detected. These results showed that the expression of ESR1-36 is regulated by EGFR, and that both act in tumor progression. Thus, the aim this study is to investigate the signaling crosstalk of ESR1-36 and EGFR in androgen-independent prostatic cancer cells. We will perform the Knockdown of ESR1-36 in the PC-3 and DU-145 cell lines and evaluate the expression of EGFR and intracellular signaling pathways involved in prostate cancer. We believe that this study will provide a better understanding of the disease, contributing to the development of specific therapies and the discovery of biomarkers.