Allopregnanolone promotes proliferation and differential gene expression in human glioblastoma cells. 2017

Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico.

Allopregnanolone (3α-THP) is one of the main reduced progesterone (P4) metabolites that is recognized as a neuroprotective and myelinating agent. 3α-THP also induces proliferation of different neural cells. It has been shown that P4 favors the progression of glioblastomas (GBM), the most common and aggressive primary brain tumors. However, the role of 3α-THP in the growth of GBMs is unknown. Here, we studied the effects of 3α-THP on the number of cells, proliferation and gene expression in U87 cell line derived from a human GBM. 3α-THP (10, 100nM and 1μM) increased the number of U87 cells, and at 10nM exerted a similar increase in both the number of total and proliferative U87 cells as compared with P4 (10nM). Interestingly, finasteride (F; 100nM), an inhibitor of 5α-reductase (5αR), an enzyme necessary to metabolize P4 and produce 3α-THP, blocked the increase in the number of U87 cells induced by P4. By using RT-qPCR, we determined that U87 cells express 5α-R isoenzymes 1 and 2 (5αR1 and 5αR2), being 5αR1 the predominant one in these cells. 3α-THP (10nM) increased the expression of TGFβ1, EGFR, VEGF and cyclin D1 genes. P4 increased TGFβ1 and EGFR expression, and this effect was blocked by F. These data provide evidence that P4, through its metabolite 3α-THP, can promote in part cell proliferation of human GBM cells by changing the expression of genes involved in tumor progression.

UI MeSH Term Description Entries
D011280 Pregnanolone A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties. Eltanolone,3 alpha, 5 beta-Tetrahydroprogesterone,3 alpha-Hydroxy-5 alpha-pregnan-20-one,3 alpha-Hydroxy-5 beta-pregnan-20-one,3-Hydroxypregnan-20-one,3beta-Hydroxy-5alpha-pregnan-20-one,Allopregnan-3 beta-ol-20-one,Allopregnanolone,Epipregnanolone,Pregnan-3alpha-ol-20-one,Pregnanolone, (3alpha)-isomer,Pregnanolone, (3alpha, 5beta, 17-alpha)-isomer,Pregnanolone, (3alpha,5alpha)-isomer,Pregnanolone, (3alpha,5beta)-isomer,Pregnanolone, (3beta)-isomer,Pregnanolone, (3beta, 5alpha)-isomer,Pregnanolone, (3beta, 5alpha, 17alpha)-isomer,Pregnanolone, (3beta, 5alpha, 8alpha, 17beta)-isomer,Pregnanolone, (3beta, 5beta)-isomer,Pregnanolone, (3beta, 5beta, 17alpha)-isomer,Pregnanolone, (3beta, 5beta,14beta)-isomer,Pregnanolone, (5alpha)-isomer,Sepranolone,3 Hydroxypregnan 20 one,3 alpha Hydroxy 5 alpha pregnan 20 one,3 alpha Hydroxy 5 beta pregnan 20 one,3 alpha, 5 beta Tetrahydroprogesterone,3beta Hydroxy 5alpha pregnan 20 one,Allopregnan 3 beta ol 20 one,Pregnan 3alpha ol 20 one,alpha-Hydroxy-5 alpha-pregnan-20-one, 3,alpha-Hydroxy-5 beta-pregnan-20-one, 3,alpha-pregnan-20-one, 3 alpha-Hydroxy-5,beta-ol-20-one, Allopregnan-3,beta-pregnan-20-one, 3 alpha-Hydroxy-5
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D042944 Cholestenone 5 alpha-Reductase An oxidoreductase that catalyzes the conversion of 3-oxo-delta4 steroids into their corresponding 5alpha form. It plays an important role in the conversion of TESTOSTERONE into DIHYDROTESTOSTERONE and PROGESTERONE into DIHYDROPROGESTERONE. 4-Ene Steroid 5 alpha-Reductase,5 alpha-Reductase,4 Ene Steroid 5 alpha Reductase,5 alpha Reductase,5 alpha-Reductase, Cholestenone,Cholestenone 5 alpha Reductase,alpha-Reductase, Cholestenone 5
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D053773 Transforming Growth Factor beta1 A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME. TGF-beta1,Transforming Growth Factor-beta1,TGF-beta-1,TGF-beta1 Latency-Associated Protein,TGF-beta1LAP,Transforming Growth Factor beta 1 Latency Associated Peptide,Transforming Growth Factor beta I,Latency-Associated Protein, TGF-beta1,TGF beta 1,TGF beta1 Latency Associated Protein,TGF beta1LAP

Related Publications

Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
May 2005, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
February 2022, Alternative therapies in health and medicine,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
November 2020, Steroids,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
November 2017, Oncology letters,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
April 2022, International journal of molecular sciences,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
January 2015, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
January 2012, Neuroscience,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
August 2016, Molecular medicine reports,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
October 2017, Oncogene,
Carmen J Zamora-Sánchez, and Valeria Hansberg-Pastor, and Ivan Salido-Guadarrama, and Mauricio Rodríguez-Dorantes, and Ignacio Camacho-Arroyo
September 2015, Biological trace element research,
Copied contents to your clipboard!