The Role of mPRδ and mPRε in Human Glioblastoma Cells: Expression, Hormonal Regulation, and Possible Clinical Outcome
The Role of mPRδ and mPRε in Human Glioblastoma Cells: Expression, Hormonal Regulation, and Possible Clinical Outcome
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DOI：
10.1007/s12672-020-00381-7
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发表时间：
2020-02-20
影响因子：
3
通讯作者：
Camacho-Arroyo, Ignacio
中科院分区：
文献类型：
--
作者：
Del Moral-Morales, Aylin;Carlos Gonzalez-Orozco, Juan;Camacho-Arroyo, Ignacio
Glioblastomas (GBM) are the most frequent and aggressive primary tumor of the central nervous system. In recent years, it has been proposed that sex hormones such as progesterone play an essential role in GBM biology. Membrane progesterone receptors (mPRs) are a group of G protein-coupled receptors with a wide distribution and multiple functions in the organism. There are five mPRs subtypes described in humans: mPR alpha, mPR beta, mPR gamma, mPR delta, and mPR epsilon. It has been reported that human-derived GBM cells express the mPR alpha, mPR beta, and mPR gamma subtypes, and that progesterone promotes GBM progression in part by mPR alpha specific activation; however, it is still unknown if mPR delta and mPR epsilon are also expressed in this type of tumor cells. In this study, we characterized the expression and hormonal regulation of mPR delta and mPR epsilon in human GBM cells. We also analyzed a set of biopsies from TCGA. We found that the expression of these receptors is dependent on the tumor's grade and that mPR delta expression is directly correlated to patients' survival while the opposite is observed for mPR epsilon. By RT-qPCR, Western blot, and immunofluorescence, the expression of mPR delta and mPR epsilon was detected for the first time in human GBM cells. An in silico analysis showed possible progesterone response elements in the promoter regions of mPR delta and mPR epsilon, and progesterone treatments downregulated the expression of these receptors. Our results suggest that mPR delta and mPR epsilon are expressed in human GBM cells and that they are relevant to GBM biology.
