POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma Tumor Cells

Author(s)

Franca, Monica Malheiros ; Ferraz-de-Souza, Bruno ; Lerario, Antonio Marcondes ; Barisson Villares Fragoso, Maria Candida ; Pacicco Lotfi, Claudimara Ferini

• Document type: Journal article
• Source: BIOMED RESEARCH INTERNATIONAL; v. 2015, p. 9-pg., 2015-01-01.

Abstract

POD-1/TCF21 may play a crucial role in adrenal and gonadal homeostasis and represses Sf-1/SF-1 expression in adrenocortical tumor cells. SF-1 and LRH-1 are members of the Fzt-F1 subfamily of nuclear receptors. LRH-1 is involved in several biological processes, and both LRH-1 and its repressor SHP are involved in many types of cancer. In order to assess whether POD-1 can regulate LRH-1 via the same mechanism that regulates SF-1, we analyzed the endogenous mRNA levels of POD-1, SHP, and LRH-1 in hepatocarcinoma and adrenocortical tumor cells using qRT-PCR. Hereafter, these tumor cells were transiently transfected with pCMVMyc Pod-1, and the effect of POD-1 overexpression on E-box elements in the LRH-1 and SHP promoter region were analyzed by ChIP assay. Also, Cyclin E1 protein expression was analyzed to detect cell cycle progression. We found that POD-1 overexpression significantly decreased SHP/SHP mRNA and protein levels through POD-1 binding to the E-box sequence in the SHP promoter. Decreased SHP expression affected LRH-1 regulation and increased Cyclin E1. These findings show that POD-1/TCF21 regulates SF-1 and LRH-1 by distinct mechanisms, contributing to the understanding of POD-1 involvement and its mechanisms of action in adrenal and liver tumorigenesis, which could lead to the discovery of relevant biomarkers. (AU)

• FAPESP's process: 11/07656-3 - Study the regulation of transcription factors SF-1 and LRH-1 in normal and tumor adrenal cells
• Grantee: Claudimara Ferini Pacicco Lotfi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/21839-6 - Study of cell cycle of adrenocortical tumor cells: analysis of oncogenes and tumor suppressor genes expression, and proliferation through the chemotherapeutic drugs action
• Grantee: Claudimara Ferini Pacicco Lotfi
• Support Opportunities: Regular Research Grants