Characterization of FOXO3a expression in uterine leiomyoma and leiomyosarcoma cells

• Grant number: 18/21616-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2019
• End date: December 31, 2019
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Kátia Cândido Carvalho
• Grantee: Dara Oliveira Ferreira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Among the uterine sarcomas, leiomyosarcoma (LMS) is the most common, with high rates of metastasis and relapse, even when diagnosed in early stages. It is a mesenchymal tumor that appears in the patients myometrium and presents high morbidity and mortality rates due to its clinical characteristics and histological complexity. The standard treatment for these tumors is surgery, because chemotherapy and radiotherapy have no impact on patient survival. Given the rarity and aggressiveness of LMS, to date, there is no consensus regarding a specific and less invasive treatment. All these aspects reinforce the need for new therapeutic strategies for these neoplasms. In this context, several studies have demonstrated that the FOXO3A transcription factor plays a significant role in cell regulation, acting as a tumor suppressor, where its inactivation or loss of expression is associated with the formation and growth of tumors. However, recent results from our research group point to FOXO3A with increased expression in mesenchymal tumors of the uterus, compared to normal adjacent myometrium. In addition, its expression increased according to the malignant potential of the tumor (from leiomyomas to LMS). This work is part of a larger project that aims to evaluate in vitro the effects of FOXO3A restoration and inhibition in these tumors with the objective of characterizing the expression profile of the FOXO3A transcription factor in cells of myometrium, leiomyoma and leiomyosarcoma. For this, myometrium (ATCC PCS-460-011), leiomyoma (THESCs-CRL-4003) and leiomyosarcoma (SK-UT-1-HTB-114) cells will initially be characterized for their expression profile of FOXO3A, by Western blot and real-time PCR. In parallel will be performed analyses in expression profile of FOXO3A and Phosphorylated FOXO3A in patient samples.