Testosterone Promotes Glioblastoma Cell Proliferation, Migration, and Invasion Through Androgen Receptor Activation.

Glioblastomas (GBM) are the most frequent and aggressive human brain tumors due to their high capacity to migrate and invade normal brain tissue. Epidemiological data report that GBM occur in a greater proportion in men than in women (3:2), suggesting the participation of sex hormones in the development of these tumors. It has been reported an increase in testosterone (T) levels in patients with GBM.

Activation of membrane progesterone receptor-alpha increases proliferation, migration, and invasion of human glioblastoma cells.

Background And Aims: Glioblastoma is the most frequent and aggressive brain tumor due to its high capacity to migrate and invade normal brain tissue. The steroid hormone progesterone (P4) contributes to the progression of glioblastoma by promoting proliferation, migration, and cellular invasion through the activation of its intracellular receptor (PR). However, the use of PR antagonist RU486 partially blocks the effects of P4, suggesting the participation of signaling pathways such as those mediated by membrane receptors to P4 (mPRs).

Allopregnanolone Alters the Gene Expression Profile of Human Glioblastoma Cells.

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.

Expression of sex hormone receptors in the brain of male and female newly hatched chicks.

Chromosomal sex and steroid hormones play a determining role in brain sexual differentiation during chick embryonic development. Hormone effects on the brain are associated with the expression pattern of their intracellular receptors, which is sexually dimorphic in many species. We determined by Western blot the content of progesterone, estrogen, and androgen receptors (PR-A and PR-B, ERα, and AR, respectively) in the cortex, cerebellum, tectum, and hypothalamus of female and male newly hatched chicks.

Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells.

Progesterone-induced blocking factor (PIBF) is a progesterone (P) regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas.

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

Allopregnanolone (3α-THP) is one of the main reduced progesterone (P) metabolites that is recognized as a neuroprotective and myelinating agent. 3α-THP also induces proliferation of different neural cells. It has been shown that P favors the progression of glioblastomas (GBM), the most common and aggressive primary brain tumors.

The interplay between intracellular progesterone receptor and PKC plays a key role in migration and invasion of human glioblastoma cells.

Intracellular progesterone receptors (PRs) and protein kinases C (PKCs) are known regulators of cancer cell proliferation and metastasis. Both PRs and PKCs are found overexpressed in grade IV human astrocytomas, also known as glioblastomas, which are the most frequent and aggressive brain tumors. In the present study, we investigated whether PR activation by PKC induces the migration and invasion of glioblastoma derived cell lines and if PKCα and δ isoforms are involved in PR activation.

CCAAT/enhancer binding protein β negatively regulates progesterone receptor expression in human glioblastoma cells.

Many progesterone (P4) actions are mediated by its intracellular receptor (PR), which has two isoforms (PR-A and PR-B) differentially transcribed from separate promoters of a single gene. In glioblastomas, the most frequent and aggressive brain tumors, PR-B is the predominant isoform. In an in silico analysis we showed putative CCAAT/Enhancer Binding Protein (C/EBP) binding sites at PR-B promoter.

Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells.

Astrocytomas are the most common and aggressive primary brain tumors in humans. Invasiveness of these tumors has been attributed in part to deregulation of cell motility-dependent cytoskeletal dynamics that involves actin-binding proteins such as cofilin. Progesterone (P4) has been found to induce migration and invasion of cells derived from breast cancer and endothelium.

Sex Hormones Regulate Cytoskeletal Proteins Involved in Brain Plasticity.

In the brain of female mammals, including humans, a number of physiological and behavioral changes occur as a result of sex hormone exposure. Estradiol and progesterone regulate several brain functions, including learning and memory. Sex hormones contribute to shape the central nervous system by modulating the formation and turnover of the interconnections between neurons as well as controlling the function of glial cells.

Expression and hormonal regulation of membrane progesterone receptors in human astrocytoma cells.

Progesterone (P) participates in the regulation of the growth of several tumors, including astrocytomas, the most common and malignant human brain tumors. It has been reported that P induces astrocytomas growth in part by its interaction with its intracellular receptors (PR). Recently, it has been reported that membrane progesterone receptors (mPRs) are expressed in ovarian and breast cancer cells, and that P could exert some actions through these receptors, however, it is unknown whether mPRs are expressed in astrocytomas.

C/EBPβ Isoforms Expression in the Rat Brain during the Estrous Cycle.

The CCAAT/enhancer-binding protein beta (C/EBPβ) is a transcription factor expressed in different areas of the brain that regulates the expression of several genes involved in cell differentiation and proliferation. This protein has three isoforms (LAP1, LAP2, and LIP) with different transcription activation potential. The role of female sex hormones in the expression pattern of C/EBPβ isoforms in the rat brain has not yet been described.

PKCα and PKCδ activation regulates transcriptional activity and degradation of progesterone receptor in human astrocytoma cells.

Progesterone regulates cancer cell proliferation and invasion through its receptors (PR-A and PR-B), whose phosphorylation modifies their transcriptional activity and induce their degradation. We identified by in silico analysis a putative residue (Ser400) in PR that might be phosphorylated by protein kinase C (PKC), a family of enzymes involved in the proliferation and infiltration of astrocytomas, the most frequent and aggressive brain tumors. A grade III human astrocytoma-derived cell line was used to study the role of PKC in PR phosphorylation, transcriptional activity, and degradation.

DNA methylation analysis of steroid hormone receptor genes.

Steroid hormone receptors (SHR) are important transcription factors for regulating different physiological and pathological processes. Their altered expression has been strongly associated to cancer progression. Epigenetic marks such as DNA methylation have been proposed as one of the regulatory mechanisms for SHR expression in cancer.

The role of DNA methylation and histone acetylation in the regulation of progesterone receptor isoforms expression in human astrocytoma cell lines.

Many progesterone (P4) effects are mediated by its intracellular receptor (PR), which has two isoforms, PR-A and PR-B, each of them with different function and regulation. Differential PR expression in cancer cells has been associated to a PR isoform-specific promoter methylation. In astrocytomas, the most frequent and aggressive brain tumors, PR isoforms expression is directly correlated to the tumor's evolution grade.

Estradiol increases cell growth in human astrocytoma cell lines through ERα activation and its interaction with SRC-1 and SRC-3 coactivators.

Estradiol (E2) regulates several cellular functions through the interaction with estrogen receptor subtypes, ERα and ERβ, which present different functional and regulation properties. ER subtypes have been identified in human astrocytomas, the most common and aggressive primary brain tumors. We studied the role of ER subtypes in cell growth of two human astrocytoma cell lines derived from tumors of different evolution grades: U373 and D54 (grades III and IV, respectively).