1,25(OH)2D3 and Prostate Cancer : The Effects on cAMP/PKA-dependent Gene Expression in LnCaP cells

University essay from Högskolan i Skövde/Institutionen för vård och natur

Author: Niklas Bergsten; [2010]

Keywords: prostate cancer; vitamin D; Vitamin D3; cAMP; PKA;

Abstract: Prostate cancer is the leading male cancer form i Sweden and maybe worldwide as well. Vitamin D is synthesized in the skin following the exposure to sunlight. Researcers have long been aware of the positive effect that vitamin D3 has on prostate tumour growth. 1,25(OH)2D3 have for a long time been the target of these studies and have shown good results. The steroid hormone induces cAMP accumulation and activiates the cAMP dependent protein kinaseA (PKA). PKA is then able to activate a transcription regulating protein. 1,25(OH)2D3 is known to cause LNCaP cells to accumulate in the G1 phase ofthe cell cycle. It has also been shown that 1,25(OH)2D3 is under negativefeedback control via 24-hydroxylase. In this study, PKA activity was observed by transfecting LNCaP cells with a viral vector carrying firefly and Renillaluciferase genes. The successfully transfected LNCaP cells would then express luciferase as a response to PKA gene expression. The LNCaP cells were then treated with 1,25(OH)2D3 and GDP-β-S (100μM), a G-protein coupled receptorinhibitor, in order to examine if 1,25(OH)2D3 regulate PKA dependent gene expression through a G-protein coupled receptor. The study could show that 1,25(OH)2D3 regulate gene expression in LNCaP cells through a PKAdependent pathway. Furthermore, the PKA dependent gene expression was demonstrated to be independent of G-protein coupled recpetor activation.

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