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

• Published in: BioMed research international Vol. 2015; no. 2015; pp. 1 - 9
• Main Authors: Fragoso, Maria Candida Barisson Villares, Lerario, Antonio Marcondes, Ferraz-de-Souza, Bruno, França, Monica Malheiros, Lotfi, Claudimara Ferini Pacicco
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2015; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - pathology; Adrenal glands; Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cancer cells; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell cycle; Cell Cycle - genetics; Cell growth; Cell Line, Tumor; Chromatin - metabolism; Colleges & universities; Cyclin E - metabolism; Deoxyribonucleic acid; DNA; Down-Regulation - genetics; E-Box Elements - genetics; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Hepatoma; Homeostasis; Humans; Laboratories; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Mice; Molecular Sequence Data; Observations; Phase transitions; Protein Binding - genetics; Proteins; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Regulation; Reproducibility of Results; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumorigenesis
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2015/841784

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 pCMVMycPod-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.