Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), 04510 Mexico City, Mexico.
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), 04510 Mexico City, Mexico.
Int J Mol Sci. 2018 Mar 15;19(3):864. doi: 10.3390/ijms19030864.
Glioblastomas (GBM) are the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3α-THP) similarly promotes cell proliferation in the U87 human GBM cell line. Here, we evaluated global changes in gene expression of U87 cells treated with 3α-THP, P4, and the 5α-reductase inhibitor, finasteride (F). 3α-THP modified the expression of 137 genes, while F changed 90. Besides, both steroids regulated the expression of 69 genes. After performing an over-representation analysis of gene ontology terms, we selected 10 genes whose products are cytoskeleton components, transcription factors, and proteins involved in the maintenance of DNA stability and replication to validate their expression changes by RT-qPCR. 3α-THP up-regulated six genes, two of them were also up-regulated by F. Two genes were up-regulated by P4 alone, however, such an effect was blocked by F when cells were treated with both steroids. The remaining genes were regulated by the combined treatments of 3α-THP + F or P4 + F. An in-silico analysis revealed that promoters of the six up-regulated genes by 3α-THP possess cyclic adenosine monophosphate (cAMP) responsive elements along with CCAAT/Enhancer binding protein alpha (CEBPα) binding sites. These findings suggest that P4 and 3α-THP regulate different sets of genes that participate in the growth of GBMs.
脑胶质瘤（GBM）是最常见和最具侵袭性的脑肿瘤。在这些恶性肿瘤中，孕酮（P4）促进增殖、迁移和侵袭。P4 的代谢产物孕烷醇酮（3α-THP）同样促进 U87 人 GBM 细胞系的细胞增殖。在这里，我们评估了用 3α-THP、P4 和 5α-还原酶抑制剂非那雄胺（F）处理的 U87 细胞的基因表达的全局变化。3α-THP 改变了 137 个基因的表达，而 F 改变了 90 个。此外，两种甾体激素调节了 69 个基因的表达。在对基因本体术语的过表达分析后，我们选择了 10 个基因，其产物是细胞骨架成分、转录因子和参与 DNA 稳定性和复制维持的蛋白质，通过 RT-qPCR 验证其表达变化。3α-THP 上调了 6 个基因，其中 2 个基因也被 F 上调。P4 单独上调了 2 个基因，但当细胞用两种甾体激素处理时，这种作用被 F 阻断。其余基因受 3α-THP+F 或 P4+F 的联合处理调节。计算机分析显示，3α-THP 上调的 6 个基因的启动子具有环磷酸腺苷（cAMP）反应元件，以及 CCAAT/增强子结合蛋白α（CEBPα）结合位点。这些发现表明，P4 和 3α-THP 调节不同的基因集，这些基因参与 GBM 的生长。
