Calcipotriol Inhibits Autocrine Phosphorylation of EGF Receptor in a Calcium-Dependent Manner, a Possible Mechanism for Its Inhibition of Cell Proliferation and Stimulation of Cell Differentiation
We report in this study that proliferation inhibition of SCC13 cells by calcipotriol was possibly mediated by its inhibitory effect on autocrine activation of EGF receptor. Based on MTT assay, PCNA staining, DAPI staining, and involucrin immunocytochemical staining, we showed that calcipotriol inhib...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2001-06, Vol.284 (2), p.419-425 |
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| creator | Lee, EunAh Jeon, Sang-Hak Youn Yi, Jae Jae Jin, Yong Sook Son, Young |
| description | We report in this study that proliferation inhibition of SCC13 cells by calcipotriol was possibly mediated by its inhibitory effect on autocrine activation of EGF receptor. Based on MTT assay, PCNA staining, DAPI staining, and involucrin immunocytochemical staining, we showed that calcipotriol inhibited cell growth and stimulated differentiation but did not induce apoptosis. Western blot analysis of concanavalin-A-bound fraction demonstrated that calcipotriol specifically dephosphorylated 170- and 66-kDa polypeptides from 8 h posttreatment and complete dephosphorylation was observed at 12 h posttreatment. The 170- and 66-kDa polypeptides were confirmed as EGF receptor and Shc, respectively. Calcipotriol-mediated EGF receptor dephosphorylation required the presence of extracellular calcium. Similar kinetics of the dephosphorylation was also observed in HaCaT cells cultured in medium of high calcium concentration. By BrdU labeling, we also showed calcium dependency of calcipotriol for the inhibition of cell proliferation. Therefore, EGF receptor deactivation by calcipotriol might be a mechanism of action for the inhibition of cell proliferation and the stimulation of differentiation in SCC13 cell and HaCaT cells. |
| doi_str_mv | 10.1006/bbrc.2001.4943 |
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Based on MTT assay, PCNA staining, DAPI staining, and involucrin immunocytochemical staining, we showed that calcipotriol inhibited cell growth and stimulated differentiation but did not induce apoptosis. Western blot analysis of concanavalin-A-bound fraction demonstrated that calcipotriol specifically dephosphorylated 170- and 66-kDa polypeptides from 8 h posttreatment and complete dephosphorylation was observed at 12 h posttreatment. The 170- and 66-kDa polypeptides were confirmed as EGF receptor and Shc, respectively. Calcipotriol-mediated EGF receptor dephosphorylation required the presence of extracellular calcium. Similar kinetics of the dephosphorylation was also observed in HaCaT cells cultured in medium of high calcium concentration. By BrdU labeling, we also showed calcium dependency of calcipotriol for the inhibition of cell proliferation. Therefore, EGF receptor deactivation by calcipotriol might be a mechanism of action for the inhibition of cell proliferation and the stimulation of differentiation in SCC13 cell and HaCaT cells.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.2001.4943</identifier><identifier>PMID: 11394895</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>1,25-dihydroxyvitamin D3 ; Adaptor Proteins, Signal Transducing ; Adaptor Proteins, Vesicular Transport ; Antineoplastic Agents - pharmacology ; Apoptosis ; Autocrine Communication - drug effects ; Blotting, Western ; Bromodeoxyuridine ; calcipotriol ; Calcitriol - analogs & derivatives ; Calcitriol - pharmacology ; calcium ; Calcium - metabolism ; Carcinoma, Squamous Cell - metabolism ; Cell Differentiation - drug effects ; Cell Division - drug effects ; Cell Line ; differentiation ; EGF receptor ; Fluorescent Dyes ; Humans ; keratinocyte ; Keratinocytes - cytology ; Keratinocytes - drug effects ; Keratinocytes - metabolism ; Phosphorylation - drug effects ; Proliferating Cell Nuclear Antigen - metabolism ; proliferation ; Protein Precursors - metabolism ; Proteins - metabolism ; Receptor, Epidermal Growth Factor - metabolism ; Shc ; Shc protein ; Shc Signaling Adaptor Proteins ; Signal Transduction - drug effects ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; Tetrazolium Salts ; Thiazoles</subject><ispartof>Biochemical and biophysical research communications, 2001-06, Vol.284 (2), p.419-425</ispartof><rights>2001 Academic Press</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c286t-77816b14ac53941f8976036f6cfcbfb73c93cd471bc99bd228625b35ee47827d3</citedby><cites>FETCH-LOGICAL-c286t-77816b14ac53941f8976036f6cfcbfb73c93cd471bc99bd228625b35ee47827d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/bbrc.2001.4943$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11394895$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, EunAh</creatorcontrib><creatorcontrib>Jeon, Sang-Hak</creatorcontrib><creatorcontrib>Youn Yi, Jae</creatorcontrib><creatorcontrib>Jae Jin, Yong</creatorcontrib><creatorcontrib>Sook Son, Young</creatorcontrib><title>Calcipotriol Inhibits Autocrine Phosphorylation of EGF Receptor in a Calcium-Dependent Manner, a Possible Mechanism for Its Inhibition of Cell Proliferation and Stimulation of Cell Differentiation</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>We report in this study that proliferation inhibition of SCC13 cells by calcipotriol was possibly mediated by its inhibitory effect on autocrine activation of EGF receptor. Based on MTT assay, PCNA staining, DAPI staining, and involucrin immunocytochemical staining, we showed that calcipotriol inhibited cell growth and stimulated differentiation but did not induce apoptosis. Western blot analysis of concanavalin-A-bound fraction demonstrated that calcipotriol specifically dephosphorylated 170- and 66-kDa polypeptides from 8 h posttreatment and complete dephosphorylation was observed at 12 h posttreatment. The 170- and 66-kDa polypeptides were confirmed as EGF receptor and Shc, respectively. Calcipotriol-mediated EGF receptor dephosphorylation required the presence of extracellular calcium. Similar kinetics of the dephosphorylation was also observed in HaCaT cells cultured in medium of high calcium concentration. By BrdU labeling, we also showed calcium dependency of calcipotriol for the inhibition of cell proliferation. Therefore, EGF receptor deactivation by calcipotriol might be a mechanism of action for the inhibition of cell proliferation and the stimulation of differentiation in SCC13 cell and HaCaT cells.</description><subject>1,25-dihydroxyvitamin D3</subject><subject>Adaptor Proteins, Signal Transducing</subject><subject>Adaptor Proteins, Vesicular Transport</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Autocrine Communication - drug effects</subject><subject>Blotting, Western</subject><subject>Bromodeoxyuridine</subject><subject>calcipotriol</subject><subject>Calcitriol - analogs & derivatives</subject><subject>Calcitriol - pharmacology</subject><subject>calcium</subject><subject>Calcium - metabolism</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Division - drug effects</subject><subject>Cell Line</subject><subject>differentiation</subject><subject>EGF receptor</subject><subject>Fluorescent Dyes</subject><subject>Humans</subject><subject>keratinocyte</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Proliferating Cell Nuclear Antigen - metabolism</subject><subject>proliferation</subject><subject>Protein Precursors - metabolism</subject><subject>Proteins - metabolism</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Shc</subject><subject>Shc protein</subject><subject>Shc Signaling Adaptor Proteins</subject><subject>Signal Transduction - drug effects</subject><subject>Src Homology 2 Domain-Containing, Transforming Protein 1</subject><subject>Tetrazolium Salts</subject><subject>Thiazoles</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuPFCEUhYnROO3o1qVh5cpqoaq6gOWk52EnM7HjI3FHgLqkMVVQAmUy_88fJt1dyayMKxL4zjmXexB6S8maEtJ91DqadU0IXbeibZ6hFSWCVDUl7XO0IoWoakF_XKBXKf0sFG078RJdUNqIlovNCv3ZqsG4KeTowoB3_uC0ywlfzTmY6Dzg_SGk6RDi46CyCx4Hi2_ubvEXMDDlELHzWOGTyTxW1zCB78Fn_KC8h_ihvO1DSk4PgB_AHJR3acS26HYlZYlbbLcwDHgfw-AsxHOY8j3-mt04P4WfqGtnC1Ny3On-NXph1ZDgzXJeou-3N9-2n6r7z3e77dV9ZWre5YoxTjtNW2U25fvUcsE60nS2M9Zoq1ljRGP6llFthNB9XUT1RjcbgJbxmvXNJXp_9p1i-DVDynJ0yZSBlIcwJ8mIqDkj9L8g5ZQT1ogCrs-giWVNEaycohtVfJSUyGPB8liwPBYsjwUXwbvFedYj9E_40mgB-BmAsojfDqJMxoE30LsIJss-uH95_wU5gbgJ</recordid><startdate>20010608</startdate><enddate>20010608</enddate><creator>Lee, EunAh</creator><creator>Jeon, Sang-Hak</creator><creator>Youn Yi, Jae</creator><creator>Jae Jin, Yong</creator><creator>Sook Son, Young</creator><general>Elsevier Inc</general><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>7QP</scope><scope>7X8</scope></search><sort><creationdate>20010608</creationdate><title>Calcipotriol Inhibits Autocrine Phosphorylation of EGF Receptor in a Calcium-Dependent Manner, a Possible Mechanism for Its Inhibition of Cell Proliferation and Stimulation of Cell Differentiation</title><author>Lee, EunAh ; Jeon, Sang-Hak ; Youn Yi, Jae ; Jae Jin, Yong ; Sook Son, Young</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-77816b14ac53941f8976036f6cfcbfb73c93cd471bc99bd228625b35ee47827d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>1,25-dihydroxyvitamin D3</topic><topic>Adaptor Proteins, Signal Transducing</topic><topic>Adaptor Proteins, Vesicular Transport</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Autocrine Communication - drug effects</topic><topic>Blotting, Western</topic><topic>Bromodeoxyuridine</topic><topic>calcipotriol</topic><topic>Calcitriol - analogs & derivatives</topic><topic>Calcitriol - pharmacology</topic><topic>calcium</topic><topic>Calcium - metabolism</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Cell Line</topic><topic>differentiation</topic><topic>EGF receptor</topic><topic>Fluorescent Dyes</topic><topic>Humans</topic><topic>keratinocyte</topic><topic>Keratinocytes - cytology</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Proliferating Cell Nuclear Antigen - metabolism</topic><topic>proliferation</topic><topic>Protein Precursors - metabolism</topic><topic>Proteins - metabolism</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Shc</topic><topic>Shc protein</topic><topic>Shc Signaling Adaptor Proteins</topic><topic>Signal Transduction - drug effects</topic><topic>Src Homology 2 Domain-Containing, Transforming Protein 1</topic><topic>Tetrazolium Salts</topic><topic>Thiazoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, EunAh</creatorcontrib><creatorcontrib>Jeon, Sang-Hak</creatorcontrib><creatorcontrib>Youn Yi, Jae</creatorcontrib><creatorcontrib>Jae Jin, Yong</creatorcontrib><creatorcontrib>Sook Son, Young</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, EunAh</au><au>Jeon, Sang-Hak</au><au>Youn Yi, Jae</au><au>Jae Jin, Yong</au><au>Sook Son, Young</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calcipotriol Inhibits Autocrine Phosphorylation of EGF Receptor in a Calcium-Dependent Manner, a Possible Mechanism for Its Inhibition of Cell Proliferation and Stimulation of Cell Differentiation</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2001-06-08</date><risdate>2001</risdate><volume>284</volume><issue>2</issue><spage>419</spage><epage>425</epage><pages>419-425</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>We report in this study that proliferation inhibition of SCC13 cells by calcipotriol was possibly mediated by its inhibitory effect on autocrine activation of EGF receptor. Based on MTT assay, PCNA staining, DAPI staining, and involucrin immunocytochemical staining, we showed that calcipotriol inhibited cell growth and stimulated differentiation but did not induce apoptosis. Western blot analysis of concanavalin-A-bound fraction demonstrated that calcipotriol specifically dephosphorylated 170- and 66-kDa polypeptides from 8 h posttreatment and complete dephosphorylation was observed at 12 h posttreatment. The 170- and 66-kDa polypeptides were confirmed as EGF receptor and Shc, respectively. Calcipotriol-mediated EGF receptor dephosphorylation required the presence of extracellular calcium. Similar kinetics of the dephosphorylation was also observed in HaCaT cells cultured in medium of high calcium concentration. By BrdU labeling, we also showed calcium dependency of calcipotriol for the inhibition of cell proliferation. Therefore, EGF receptor deactivation by calcipotriol might be a mechanism of action for the inhibition of cell proliferation and the stimulation of differentiation in SCC13 cell and HaCaT cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11394895</pmid><doi>10.1006/bbrc.2001.4943</doi><tpages>7</tpages></addata></record> |
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| subjects | 1,25-dihydroxyvitamin D3 Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport Antineoplastic Agents - pharmacology Apoptosis Autocrine Communication - drug effects Blotting, Western Bromodeoxyuridine calcipotriol Calcitriol - analogs & derivatives Calcitriol - pharmacology calcium Calcium - metabolism Carcinoma, Squamous Cell - metabolism Cell Differentiation - drug effects Cell Division - drug effects Cell Line differentiation EGF receptor Fluorescent Dyes Humans keratinocyte Keratinocytes - cytology Keratinocytes - drug effects Keratinocytes - metabolism Phosphorylation - drug effects Proliferating Cell Nuclear Antigen - metabolism proliferation Protein Precursors - metabolism Proteins - metabolism Receptor, Epidermal Growth Factor - metabolism Shc Shc protein Shc Signaling Adaptor Proteins Signal Transduction - drug effects Src Homology 2 Domain-Containing, Transforming Protein 1 Tetrazolium Salts Thiazoles |
| title | Calcipotriol Inhibits Autocrine Phosphorylation of EGF Receptor in a Calcium-Dependent Manner, a Possible Mechanism for Its Inhibition of Cell Proliferation and Stimulation of Cell Differentiation |
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