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Hagberg, Malin
Publications (2 of 2) Show all publications
Larsson, D., Hagberg, M., Nahren, M., Kjellberg, C., Senneberg, E., Tahmasebifar, N. & Johansson, V. (2008). Membrane Initiated Signaling by 1,25α-dihydroxyvitamin D3 in LNCaP Prostate Cancer Cells. Springer
Open this publication in new window or tab >>Membrane Initiated Signaling by 1,25α-dihydroxyvitamin D3 in LNCaP Prostate Cancer Cells
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2008 (English)Conference paper, Published paper (Other academic)
Abstract [en]

Prostate cancer (PC) is one of the most common cancers among men, and vitamin D and its metabolites are candidates for prevention and therapy of this disease. The vitamin D metabolites, 1, 25-dihydroxyvitamin D3 (1,25D) and 25-hydroxyvitamin D3, decreases cellular proliferation and invasiveness, and stimulates differentiation of PC cells. However, the underlying mechanisms are not fully clarified, and there is evidence that some of these effects of the vitamin D system are mediated by specific membrane-associated receptors/binding proteins in addition to its nuclear receptor, suggesting multiple regulatory pathways. The aim of the present study was to examine the role of membrane initiated pathways mediating effects of 1,25D on cell invasiveness in LNCaP cells. Treatment with 1,25D evoked a dose-dependent activation of the JNK/SAPK MAPK signaling pathways within 10 min, demonstrating membrane initiated signaling of 1,25D in LNCaP cells. Furthermore, treatment with 1,25D decreased LNCaP cell invasiveness by approximately 20% after 48h. Using an inhibitor (SP600125) for the JNK/SAPK MAPK signaling pathway in combination with 1,25D on LNCaP cells, the inhibitory action of 1,25D on invasiveness was eliminated. In conclusion, 1,25D decrease invasiveness of LNCaP cells by interaction with a putative membrane associated receptor, which activate membrane, initiated signaling via the JNK/SAPK MAPK signaling pathway.

Place, publisher, year, edition, pages
Springer, 2008
Series
Advances in Experimental Medicine and Biology, ISSN 0065-2598 ; 617
National Category
Medical and Health Sciences
Research subject
Medical sciences
Identifiers
urn:nbn:se:his:diva-2731 (URN)10.1007/978-0-387-69080-3 (DOI)000253701800059 ()2-s2.0-46749094667 (Scopus ID)978-0-387-69078-0 (ISBN)
Available from: 2009-02-11 Created: 2009-02-11 Last updated: 2017-11-27Bibliographically approved
Hagberg, M., Holmén, J., Olausson, J., Karlsson, S., Johansson, V. & Larsson, D. (2008). Rapid activation of JNK/SAPK in LNCaP prostate cancer cells by 1α,25-dihydroxyvitamin D3 is independent of PDIA3 (1,25-MARRS). Current Topics in Steroid Research, 5, 17-24
Open this publication in new window or tab >>Rapid activation of JNK/SAPK in LNCaP prostate cancer cells by 1α,25-dihydroxyvitamin D3 is independent of PDIA3 (1,25-MARRS)
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2008 (English)In: Current Topics in Steroid Research, ISSN 0972-4788, Vol. 5, p. 17-24Article in journal (Refereed) Published
Abstract [en]

1α,25-dihydroxyvitamin D3 (1,25D3 ) is a highly potential anti-cancerous agent for prevention and treatment of prostate cancer, the most commonly diagnosed cancer type of males in western countries. A recent study by our laboratory, demonstrates that LNCaP cancer cells treated with 1,25D3, evoked dose-dependent activation of the JNK/SAPK MAPK signaling pathway within 10 minutes after hormone treatment, indicative of membrane-initiated steroid signaling (MISS) by 1,25D3. This confirms previous reports on intestinal-, chondrocyte- and osteoblast cells, where 1,25D3 operates through pharmacologically distinct nuclear-initiated mechanisms (NISS) and plasma membrane-initiated mechanisms. NISS is mediated via the vitamin D receptor (nVDR) and MISS is mediated through 1,25D3-MARRS (PDIA3, 1,25D3-membraneassociated rapid response steroid binding protein) or nVDR. The aims of the present study were to investigate the mechanisms of MISS evoked effects on alkaline phosphatase (ALP) and activation of the JNK/SAPK by 1,25D3, and the involvement of PDIA3 in 1,25D3 initiated activation of the JNK/SAPK signaling pathway. Furthermore, 1,25D3-treated LNCaP cells were transfected with siRNA against PDIA3 and phosphorylated JNK/SAPK was estimated by western analysis. Western analysis and ALP-assays demonstrated rapid activation of both JNK/SAPK as well as ALP. Silencing of PDIA3 did not affect 1,25D3 mediated activation of JNK/SAPK, suggesting that PDIA3 is not involved in the 1,25D3-initiated activation of the JNK/SAPK signaling pathway.

Place, publisher, year, edition, pages
Research Trends, 2008
Keywords
vitamin D, MAP kinase, JNK/SAPK, VDR, PDIA3, LNCaP, prostate cancer, 1α, 25(OH)2D3, siRNA, membrane initiated steroid signaling, MISS, alkaline phosphatase
National Category
Biochemistry and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:his:diva-2429 (URN)
Available from: 2008-12-05 Created: 2008-12-05 Last updated: 2019-07-03Bibliographically approved
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