title: POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma Tumor Cells.
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 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.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Monica Malheiros
authors.initials: MM
authors.lastname: França
authors.affiliation: Laboratory of Medical Investigation 18 (LIM-18), School of Medicine, University of São Paulo, 01246-903 São Paulo, SP, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ferraz-de-Souza
authors.affiliation: Laboratory of Hormones and Molecular Genetics (LIM-42), Adrenal Unit, Division of Endocrinology, School of Medicine, University of São Paulo, 01246-903 São Paulo, SP, Brazil.
authors.forename: Antonio Marcondes
authors.initials: AM
authors.lastname: Lerario
authors.affiliation: Laboratory of Hormones and Molecular Genetics (LIM-42), Adrenal Unit, Division of Endocrinology, School of Medicine, University of São Paulo, 01246-903 São Paulo, SP, Brazil.
authors.forename: Maria Candida Barisson Villares
authors.initials: MC
authors.lastname: Fragoso
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Claudimara Ferini Pacicco
authors.initials: CF
authors.lastname: Lotfi
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D024721:E-Box Elements / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D019927:Cyclin E; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C082631:NR5A2 protein, human; C491825:TCF21 protein, human; C099713:nuclear receptor subfamily 0, group B, member 2