pod-1/tcf21 reduces shp expression, affecting lrh-1 regulation and cell cycle balance in adrenocortical and hepatocarcinoma tumor cells

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ID: 214209
2015
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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.
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frana2015biomedpod-1/tcf21 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Monica Malheiros França;Bruno Ferraz-de-Souza;Antonio Marcondes Lerario;Maria Candida Barisson Villares Fragoso;Claudimara Ferini Pacicco Lotfi
Journal spectrochimica acta - part a: molecular and biomolecular spectroscopy
Year 2015
DOI
10.1155/2015/841784
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