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Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells
•1,25 Dihydroxyvitamin D3 induces the expression of CaSR in Caco2/AQ and Coga1A cells.•TNFα is the main driver of CaSR expression in Coga1A.•In Caco2/AQ cells 1,25 dihydroxyvitamin D3 counteracts the action of TNFα and IL-6. Anti-proliferative effects of calcium in the colon are mediated, at least i...
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| Published in: | The Journal of steroid biochemistry and molecular biology 2014-10, Vol.144, p.228-231 |
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| container_title | The Journal of steroid biochemistry and molecular biology |
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| creator | Fetahu, Irfete S. Hummel, Doris M. Manhardt, Teresa Aggarwal, Abhishek Baumgartner-Parzer, Sabina Kállay, Enikő |
| description | •1,25 Dihydroxyvitamin D3 induces the expression of CaSR in Caco2/AQ and Coga1A cells.•TNFα is the main driver of CaSR expression in Coga1A.•In Caco2/AQ cells 1,25 dihydroxyvitamin D3 counteracts the action of TNFα and IL-6.
Anti-proliferative effects of calcium in the colon are mediated, at least in part, via the calcium-sensing receptor (CaSR), a vitamin D target gene. The expression of CaSR decreases during colorectal tumor progression and the mechanisms regulating its expression are poorly understood. The CaSR promoter harbors vitamin D elements responsive to 1,25-dihydroxyvitamin D3 (1,25D3) and NF-κB, STAT, and SP1 binding sites accounting for responsiveness to proinflammatory cytokines. Therefore, in the current study we investigated the impact of 1,25D3, tumor necrosis factor alpha (TNFα), and interleukin (IL)-6 on CaSR expression in a differentiated (Caco2/AQ) and in a moderately differentiated (Coga1A) colon cancer cell line. 1,25D3 induced CaSR expression in both cell lines. Treatment with TNFα was accompanied by a 134-fold induction of CaSR in Coga1A (p |
| doi_str_mv | 10.1016/j.jsbmb.2013.10.015 |
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Anti-proliferative effects of calcium in the colon are mediated, at least in part, via the calcium-sensing receptor (CaSR), a vitamin D target gene. The expression of CaSR decreases during colorectal tumor progression and the mechanisms regulating its expression are poorly understood. The CaSR promoter harbors vitamin D elements responsive to 1,25-dihydroxyvitamin D3 (1,25D3) and NF-κB, STAT, and SP1 binding sites accounting for responsiveness to proinflammatory cytokines. Therefore, in the current study we investigated the impact of 1,25D3, tumor necrosis factor alpha (TNFα), and interleukin (IL)-6 on CaSR expression in a differentiated (Caco2/AQ) and in a moderately differentiated (Coga1A) colon cancer cell line. 1,25D3 induced CaSR expression in both cell lines. Treatment with TNFα was accompanied by a 134-fold induction of CaSR in Coga1A (p<0.01). In Caco2/AQ cells the expression of CaSR was upregulated also by IL-6 (3.5-fold). Our data demonstrated transcriptional and translational activation of the CaSR by 1,25D3, TNFα, and IL-6 in a time- and cell line-dependent manner.
This article is part of a Special Issue entitled ‘16th Vitamin D Workshop’.</description><identifier>ISSN: 0960-0760</identifier><identifier>EISSN: 1879-1220</identifier><identifier>DOI: 10.1016/j.jsbmb.2013.10.015</identifier><identifier>PMID: 24176760</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>1,25-dihydroxyvitamin D3 ; Animals ; Bone Density Conservation Agents - pharmacology ; Calcitriol - pharmacology ; Calcium-sensing receptor ; Colon cancer ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - genetics ; Colonic Neoplasms - metabolism ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Inflammation ; Interleukin-6 ; Interleukin-6 - pharmacology ; Receptors, Calcium-Sensing - metabolism ; Tumor necrosis factor alpha ; Tumor Necrosis Factor-alpha - pharmacology</subject><ispartof>The Journal of steroid biochemistry and molecular biology, 2014-10, Vol.144, p.228-231</ispartof><rights>2013 The Authors</rights><rights>Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>2013 The Authors 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4075-241a3790a0316df2cee34ec075ff5778b7631d787ae78e24aa050926f04ca9c23</citedby><cites>FETCH-LOGICAL-c4075-241a3790a0316df2cee34ec075ff5778b7631d787ae78e24aa050926f04ca9c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24176760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fetahu, Irfete S.</creatorcontrib><creatorcontrib>Hummel, Doris M.</creatorcontrib><creatorcontrib>Manhardt, Teresa</creatorcontrib><creatorcontrib>Aggarwal, Abhishek</creatorcontrib><creatorcontrib>Baumgartner-Parzer, Sabina</creatorcontrib><creatorcontrib>Kállay, Enikő</creatorcontrib><title>Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells</title><title>The Journal of steroid biochemistry and molecular biology</title><addtitle>J Steroid Biochem Mol Biol</addtitle><description>•1,25 Dihydroxyvitamin D3 induces the expression of CaSR in Caco2/AQ and Coga1A cells.•TNFα is the main driver of CaSR expression in Coga1A.•In Caco2/AQ cells 1,25 dihydroxyvitamin D3 counteracts the action of TNFα and IL-6.
Anti-proliferative effects of calcium in the colon are mediated, at least in part, via the calcium-sensing receptor (CaSR), a vitamin D target gene. The expression of CaSR decreases during colorectal tumor progression and the mechanisms regulating its expression are poorly understood. The CaSR promoter harbors vitamin D elements responsive to 1,25-dihydroxyvitamin D3 (1,25D3) and NF-κB, STAT, and SP1 binding sites accounting for responsiveness to proinflammatory cytokines. Therefore, in the current study we investigated the impact of 1,25D3, tumor necrosis factor alpha (TNFα), and interleukin (IL)-6 on CaSR expression in a differentiated (Caco2/AQ) and in a moderately differentiated (Coga1A) colon cancer cell line. 1,25D3 induced CaSR expression in both cell lines. Treatment with TNFα was accompanied by a 134-fold induction of CaSR in Coga1A (p<0.01). In Caco2/AQ cells the expression of CaSR was upregulated also by IL-6 (3.5-fold). Our data demonstrated transcriptional and translational activation of the CaSR by 1,25D3, TNFα, and IL-6 in a time- and cell line-dependent manner.
This article is part of a Special Issue entitled ‘16th Vitamin D Workshop’.</description><subject>1,25-dihydroxyvitamin D3</subject><subject>Animals</subject><subject>Bone Density Conservation Agents - pharmacology</subject><subject>Calcitriol - pharmacology</subject><subject>Calcium-sensing receptor</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin-6</subject><subject>Interleukin-6 - pharmacology</subject><subject>Receptors, Calcium-Sensing - metabolism</subject><subject>Tumor necrosis factor alpha</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><issn>0960-0760</issn><issn>1879-1220</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp9UV2r1DAUDKJ416u_QJD8gO16krRN-6Ag10-4IIg-hzQ93c2aJiVpl7u_xL9r6upFX3w6MGdmDnOGkOcMdgxY_fK4O6Zu7HYcmMjIDlj1gGxYI9uCcQ4PyQbaGgqQNVyRJykdAUAIJh-TK14yWWd8Q358wf3i9GyDp2Gg8wGp0c7YZSwS-mT9nkY0OM0hUrybIqa0UrszZVteFb09nPsY7s4nO-vRevpWbKn1M0aHy3fri3pLte_pvIzZwKOJIdlEB21WQ-2mg850aoLLpkZ7g5EadC49JY8G7RI--z2vybf3777efCxuP3_4dPPmtjAlyKrIQbSQLWgQrO4HbhBFiSavhqGSsulkLVgvG6lRNshLraGCltcDlEa3hotr8vriOy3diL1BP0ft1BTtqONZBW3VvxtvD2ofTqrMLwZosoG4GKzRUsThXstArT2po_rVk1p7WsHcU1a9-PvsveZPMZnw6kLAHP5kMapkLOb_9Db3Mas-2P8e-AmBl6hc</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Fetahu, Irfete S.</creator><creator>Hummel, Doris M.</creator><creator>Manhardt, Teresa</creator><creator>Aggarwal, Abhishek</creator><creator>Baumgartner-Parzer, Sabina</creator><creator>Kállay, Enikő</creator><general>Elsevier Ltd</general><general>Pergamon</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20141001</creationdate><title>Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells</title><author>Fetahu, Irfete S. ; Hummel, Doris M. ; Manhardt, Teresa ; Aggarwal, Abhishek ; Baumgartner-Parzer, Sabina ; Kállay, Enikő</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4075-241a3790a0316df2cee34ec075ff5778b7631d787ae78e24aa050926f04ca9c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>1,25-dihydroxyvitamin D3</topic><topic>Animals</topic><topic>Bone Density Conservation Agents - pharmacology</topic><topic>Calcitriol - pharmacology</topic><topic>Calcium-sensing receptor</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin-6</topic><topic>Interleukin-6 - pharmacology</topic><topic>Receptors, Calcium-Sensing - metabolism</topic><topic>Tumor necrosis factor alpha</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fetahu, Irfete S.</creatorcontrib><creatorcontrib>Hummel, Doris M.</creatorcontrib><creatorcontrib>Manhardt, Teresa</creatorcontrib><creatorcontrib>Aggarwal, Abhishek</creatorcontrib><creatorcontrib>Baumgartner-Parzer, Sabina</creatorcontrib><creatorcontrib>Kállay, Enikő</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fetahu, Irfete S.</au><au>Hummel, Doris M.</au><au>Manhardt, Teresa</au><au>Aggarwal, Abhishek</au><au>Baumgartner-Parzer, Sabina</au><au>Kállay, Enikő</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells</atitle><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle><addtitle>J Steroid Biochem Mol Biol</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>144</volume><spage>228</spage><epage>231</epage><pages>228-231</pages><issn>0960-0760</issn><eissn>1879-1220</eissn><abstract>•1,25 Dihydroxyvitamin D3 induces the expression of CaSR in Caco2/AQ and Coga1A cells.•TNFα is the main driver of CaSR expression in Coga1A.•In Caco2/AQ cells 1,25 dihydroxyvitamin D3 counteracts the action of TNFα and IL-6.
Anti-proliferative effects of calcium in the colon are mediated, at least in part, via the calcium-sensing receptor (CaSR), a vitamin D target gene. The expression of CaSR decreases during colorectal tumor progression and the mechanisms regulating its expression are poorly understood. The CaSR promoter harbors vitamin D elements responsive to 1,25-dihydroxyvitamin D3 (1,25D3) and NF-κB, STAT, and SP1 binding sites accounting for responsiveness to proinflammatory cytokines. Therefore, in the current study we investigated the impact of 1,25D3, tumor necrosis factor alpha (TNFα), and interleukin (IL)-6 on CaSR expression in a differentiated (Caco2/AQ) and in a moderately differentiated (Coga1A) colon cancer cell line. 1,25D3 induced CaSR expression in both cell lines. Treatment with TNFα was accompanied by a 134-fold induction of CaSR in Coga1A (p<0.01). In Caco2/AQ cells the expression of CaSR was upregulated also by IL-6 (3.5-fold). Our data demonstrated transcriptional and translational activation of the CaSR by 1,25D3, TNFα, and IL-6 in a time- and cell line-dependent manner.
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| subjects | 1,25-dihydroxyvitamin D3 Animals Bone Density Conservation Agents - pharmacology Calcitriol - pharmacology Calcium-sensing receptor Colon cancer Colonic Neoplasms - drug therapy Colonic Neoplasms - genetics Colonic Neoplasms - metabolism Gene Expression Regulation, Neoplastic - drug effects Humans Inflammation Interleukin-6 Interleukin-6 - pharmacology Receptors, Calcium-Sensing - metabolism Tumor necrosis factor alpha Tumor Necrosis Factor-alpha - pharmacology |
| title | Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells |
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