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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Franca, Monica Malheiros [1] ; Ferraz-de-Souza, Bruno [2] ; Lerario, Antonio Marcondes [3] ; Barisson Villares Fragoso, Maria Candida [3] ; Pacicco Lotfi, Claudimara Ferini [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Sch Med, Lab Med Invest LIM 18 18, BR-01246903 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Sch Med, Div Endocrinol, Lab Hormones & Mol Genet LIM 42, Adrenal Unit, BR-01246903 Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: BIOMED RESEARCH INTERNATIONAL; 2015.
Citações Web of Science: 5
Resumo

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)

Processo FAPESP: 11/07656-3 - Estudo da regulação dos fatores de transcrição SF-1 e LRH-1 em células adrenais normais e tumorais
Beneficiário:Claudimara Ferini Pacicco Lotfi
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/21839-6 - Estudo do ciclo celular das células de tumores adrenocorticais: análise da expressão de oncogenes e genes supressores de tumores, e da proliferação através da ação de quimioterápicos
Beneficiário:Claudimara Ferini Pacicco Lotfi
Linha de fomento: Auxílio à Pesquisa - Regular