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Identifier

000454399

Title

Ο ρόλος του μεμβρανικού υποδοχέα ανδρογόνων OXER1 στις αλλαγές του ενδοκυττάριου ασβεστίου

Alternative Title

The role of the membrane androgen receptor OXER1 in intracellular calcium changes

Author

Κωνσταντίνου, Ευαγγελία Κ.

Thesis advisor

Σπύρος, Απόστολος
Καμπά, Μαρία-Ελένη

Reviewer

Πυρίντσος, Στέργιος

Abstract

Androgen molecules play a central role as hormonal signals in the processes of growth, differentiation and proper functioning of organisms. Androgen molecules exert their action through classical intracellular nuclear receptors or membrane androgen receptors. Androgen action via nuclear receptors has been extensively studied and mainly involves binding to gene response elements as transcription factors. Undoubted, however, is the action of androgens via membrane androgen receptors, which in many cases differs significantly from the classical action of these steroid molecules. Non-genomic actions of androgens via membrane receptors are often evident as a rapid increase in intracellular free Ca⁺² concentration is observed. Our research group has shown that membraneacting testosterone increases intracellular Ca⁺² levels in prostate cancer cells. In addition, we reported that testosterone can act through the OXER1 receptor by reversing the cAMP inhibition induced by 5-oxo-ETP. For OXER1, 5-oxo-ETE increased ERK1/2 phosphorylation rate and calcium mobilization through a signaling cascade consisting of phosphatidylinositol 3-kinase and Akt proteins in both prostate cancer cells and eosinophils. In addition, G_βγ signaling was shown to promote actin polymerization. Several mechanisms of action are involved in Ca⁺² signaling. It can trigger exocytosis within seconds, even rapid muscle contraction, but on the other side of the scale, gene transcription and cell proliferation can operate within minutes to hours. Studies have shown that intracellular Ca⁺² homeostasis is altered, affecting tumor growth, angiogenesis, proliferation and metastasis. Signaling changes in Ca⁺² concentration has become a new area of research in cancer therapy. The purpose of this master's thesis is to study the calcium signaling pathway mediated by the OXER1 receptor, to clarify and understand the process of regulating Ca⁺² signaling in cancer cells. In addition, the effects of natural products on intracellular calcium ion flux in prostate cancer cells, as well as their effects on the modification of the actin cytoskeleton, were studied.

Language

Greek, English

Subject

5-oxo-ETE

Actin cytoskeleton

Calcium signaling

Natural products

Prostate cancer

Testosterone

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