Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells
BACKGROUND Neuroendocrine (NE) differentiation in prostate cancer has been suggested to be one of the early events in the development of androgen independence. In the human prostate cancer LNCaP cell line, treatment with interleukin‐6 (IL‐6) induces NE‐like differentiation, which is similar to the p...
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| Veröffentlicht in: | The Prostate 2004-06, Vol.60 (1), p.61-67 |
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| creator | Xie, Shaozhen Lin, Hui-Kuan Ni, Jing Yang, Lin Wang, Liang di Sant'Agnese, P. Anthony Chang, Chawnshang |
| description | BACKGROUND
Neuroendocrine (NE) differentiation in prostate cancer has been suggested to be one of the early events in the development of androgen independence. In the human prostate cancer LNCaP cell line, treatment with interleukin‐6 (IL‐6) induces NE‐like differentiation, which is similar to the phenomena observed in advanced stages of prostate cancer progression. In this study, we investigate how androgen plays a role in IL‐6‐mediated NE differentiation in LNCaP cell line.
METHODS
Western blot, co‐immunoprecipitation (co‐IP), and GST pull‐down assays were performed to detect the protein expression and protein–protein interaction. PI3K kinase assay was used to measure PI3K activity.
RESULTS
Addition of androgen blocks IL‐6‐mediated PI3K activation and NE differentiation in LNCaP cells. In vivo and in vitro protein interaction assays suggested that androgen receptor (AR) can directly interact with IL‐6 transducer gp130. In addition, androgen treatment enhances the interaction between AR and gp130, interrupts the IL‐6‐induced gp130‐mediated PI3K activation, which may lead to inhibition of IL‐6‐mediated NE differentiation in LNCaP cells.
CONCLUSIONS
Our results suggest androgen and AR can regulate IL‐6‐mediated LNCaP cell NE differentiation via directly modulating the IL‐6‐PI3K pathway. © 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/pros.20048 |
| format | Article |
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Neuroendocrine (NE) differentiation in prostate cancer has been suggested to be one of the early events in the development of androgen independence. In the human prostate cancer LNCaP cell line, treatment with interleukin‐6 (IL‐6) induces NE‐like differentiation, which is similar to the phenomena observed in advanced stages of prostate cancer progression. In this study, we investigate how androgen plays a role in IL‐6‐mediated NE differentiation in LNCaP cell line.
METHODS
Western blot, co‐immunoprecipitation (co‐IP), and GST pull‐down assays were performed to detect the protein expression and protein–protein interaction. PI3K kinase assay was used to measure PI3K activity.
RESULTS
Addition of androgen blocks IL‐6‐mediated PI3K activation and NE differentiation in LNCaP cells. In vivo and in vitro protein interaction assays suggested that androgen receptor (AR) can directly interact with IL‐6 transducer gp130. In addition, androgen treatment enhances the interaction between AR and gp130, interrupts the IL‐6‐induced gp130‐mediated PI3K activation, which may lead to inhibition of IL‐6‐mediated NE differentiation in LNCaP cells.
CONCLUSIONS
Our results suggest androgen and AR can regulate IL‐6‐mediated LNCaP cell NE differentiation via directly modulating the IL‐6‐PI3K pathway. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.20048</identifier><identifier>PMID: 15129430</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>androgen ; androgen receptor ; Blotting, Western ; Cell Differentiation ; Contactins ; differentiation ; Disease Progression ; Drug Resistance, Neoplasm ; Humans ; IL-6 ; Interleukin-6 - pharmacology ; Male ; Neural Cell Adhesion Molecules - pharmacology ; Phosphatidylinositol 3-Kinases - pharmacology ; PI3K ; Plasmids ; prostate cancer ; Prostatic Neoplasms - pathology ; Receptors, Androgen - drug effects ; Receptors, Androgen - physiology ; Signal Transduction ; Tumor Cells, Cultured</subject><ispartof>The Prostate, 2004-06, Vol.60 (1), p.61-67</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3638-45f061fcf54525a79eca873cfd0bd7c33636556f0498d39b44ed336985eb5ff73</citedby><cites>FETCH-LOGICAL-c3638-45f061fcf54525a79eca873cfd0bd7c33636556f0498d39b44ed336985eb5ff73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.20048$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.20048$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15129430$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xie, Shaozhen</creatorcontrib><creatorcontrib>Lin, Hui-Kuan</creatorcontrib><creatorcontrib>Ni, Jing</creatorcontrib><creatorcontrib>Yang, Lin</creatorcontrib><creatorcontrib>Wang, Liang</creatorcontrib><creatorcontrib>di Sant'Agnese, P. Anthony</creatorcontrib><creatorcontrib>Chang, Chawnshang</creatorcontrib><title>Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>BACKGROUND
Neuroendocrine (NE) differentiation in prostate cancer has been suggested to be one of the early events in the development of androgen independence. In the human prostate cancer LNCaP cell line, treatment with interleukin‐6 (IL‐6) induces NE‐like differentiation, which is similar to the phenomena observed in advanced stages of prostate cancer progression. In this study, we investigate how androgen plays a role in IL‐6‐mediated NE differentiation in LNCaP cell line.
METHODS
Western blot, co‐immunoprecipitation (co‐IP), and GST pull‐down assays were performed to detect the protein expression and protein–protein interaction. PI3K kinase assay was used to measure PI3K activity.
RESULTS
Addition of androgen blocks IL‐6‐mediated PI3K activation and NE differentiation in LNCaP cells. In vivo and in vitro protein interaction assays suggested that androgen receptor (AR) can directly interact with IL‐6 transducer gp130. In addition, androgen treatment enhances the interaction between AR and gp130, interrupts the IL‐6‐induced gp130‐mediated PI3K activation, which may lead to inhibition of IL‐6‐mediated NE differentiation in LNCaP cells.
CONCLUSIONS
Our results suggest androgen and AR can regulate IL‐6‐mediated LNCaP cell NE differentiation via directly modulating the IL‐6‐PI3K pathway. © 2004 Wiley‐Liss, Inc.</description><subject>androgen</subject><subject>androgen receptor</subject><subject>Blotting, Western</subject><subject>Cell Differentiation</subject><subject>Contactins</subject><subject>differentiation</subject><subject>Disease Progression</subject><subject>Drug Resistance, Neoplasm</subject><subject>Humans</subject><subject>IL-6</subject><subject>Interleukin-6 - pharmacology</subject><subject>Male</subject><subject>Neural Cell Adhesion Molecules - pharmacology</subject><subject>Phosphatidylinositol 3-Kinases - pharmacology</subject><subject>PI3K</subject><subject>Plasmids</subject><subject>prostate cancer</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Receptors, Androgen - drug effects</subject><subject>Receptors, Androgen - physiology</subject><subject>Signal Transduction</subject><subject>Tumor Cells, Cultured</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u1DAURi0EokNhwwMgr1ggpdixHSdLmLZDxagdyt_ScuzrkWnGKXYCzDv0oXHIFHasrnV17tHnD6HnlJxQQsrXt7FPJyUhvH6AFpQ0sshv8RAtSClJwSmTR-hJSt8IyTgpH6MjKmjZcEYW6O4atmOnB98H3DvswwCxg_HGh6IqdmC9HsDizQV7j7UZ_I-Z1MHiAGPsIdjeRB8AW-8cRAiDn5F2P1Gx30LAyW-D7nzYZj-e0g7Zio0OBiJeXy71BhvouvQUPXK6S_DsMI_R5_OzT8t3xfpqdbF8sy4Mq1hdcOFIRZ1xgotSaNmA0bVkxlnSWmlYhiohKkd4U1vWtJyDzcumFtAK5yQ7Ri9nb87yfYQ0qJ1PUwIdoB-TkrTJ_TCawVczaHLoFMGp2-h3Ou4VJWrqXk2_UX-6z_CLg3Vsc3P_0EPZGaAz8NN3sP-PSm2urz7eS4v5xqcBfv290fFGVZJJob5ertSH07VcvT39ojj7DSZVoIc</recordid><startdate>20040615</startdate><enddate>20040615</enddate><creator>Xie, Shaozhen</creator><creator>Lin, Hui-Kuan</creator><creator>Ni, Jing</creator><creator>Yang, Lin</creator><creator>Wang, Liang</creator><creator>di Sant'Agnese, P. Anthony</creator><creator>Chang, Chawnshang</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>20040615</creationdate><title>Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells</title><author>Xie, Shaozhen ; Lin, Hui-Kuan ; Ni, Jing ; Yang, Lin ; Wang, Liang ; di Sant'Agnese, P. Anthony ; Chang, Chawnshang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3638-45f061fcf54525a79eca873cfd0bd7c33636556f0498d39b44ed336985eb5ff73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>androgen</topic><topic>androgen receptor</topic><topic>Blotting, Western</topic><topic>Cell Differentiation</topic><topic>Contactins</topic><topic>differentiation</topic><topic>Disease Progression</topic><topic>Drug Resistance, Neoplasm</topic><topic>Humans</topic><topic>IL-6</topic><topic>Interleukin-6 - pharmacology</topic><topic>Male</topic><topic>Neural Cell Adhesion Molecules - pharmacology</topic><topic>Phosphatidylinositol 3-Kinases - pharmacology</topic><topic>PI3K</topic><topic>Plasmids</topic><topic>prostate cancer</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Receptors, Androgen - drug effects</topic><topic>Receptors, Androgen - physiology</topic><topic>Signal Transduction</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xie, Shaozhen</creatorcontrib><creatorcontrib>Lin, Hui-Kuan</creatorcontrib><creatorcontrib>Ni, Jing</creatorcontrib><creatorcontrib>Yang, Lin</creatorcontrib><creatorcontrib>Wang, Liang</creatorcontrib><creatorcontrib>di Sant'Agnese, P. Anthony</creatorcontrib><creatorcontrib>Chang, Chawnshang</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xie, Shaozhen</au><au>Lin, Hui-Kuan</au><au>Ni, Jing</au><au>Yang, Lin</au><au>Wang, Liang</au><au>di Sant'Agnese, P. Anthony</au><au>Chang, Chawnshang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2004-06-15</date><risdate>2004</risdate><volume>60</volume><issue>1</issue><spage>61</spage><epage>67</epage><pages>61-67</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><abstract>BACKGROUND
Neuroendocrine (NE) differentiation in prostate cancer has been suggested to be one of the early events in the development of androgen independence. In the human prostate cancer LNCaP cell line, treatment with interleukin‐6 (IL‐6) induces NE‐like differentiation, which is similar to the phenomena observed in advanced stages of prostate cancer progression. In this study, we investigate how androgen plays a role in IL‐6‐mediated NE differentiation in LNCaP cell line.
METHODS
Western blot, co‐immunoprecipitation (co‐IP), and GST pull‐down assays were performed to detect the protein expression and protein–protein interaction. PI3K kinase assay was used to measure PI3K activity.
RESULTS
Addition of androgen blocks IL‐6‐mediated PI3K activation and NE differentiation in LNCaP cells. In vivo and in vitro protein interaction assays suggested that androgen receptor (AR) can directly interact with IL‐6 transducer gp130. In addition, androgen treatment enhances the interaction between AR and gp130, interrupts the IL‐6‐induced gp130‐mediated PI3K activation, which may lead to inhibition of IL‐6‐mediated NE differentiation in LNCaP cells.
CONCLUSIONS
Our results suggest androgen and AR can regulate IL‐6‐mediated LNCaP cell NE differentiation via directly modulating the IL‐6‐PI3K pathway. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15129430</pmid><doi>10.1002/pros.20048</doi><tpages>7</tpages></addata></record> |
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| subjects | androgen androgen receptor Blotting, Western Cell Differentiation Contactins differentiation Disease Progression Drug Resistance, Neoplasm Humans IL-6 Interleukin-6 - pharmacology Male Neural Cell Adhesion Molecules - pharmacology Phosphatidylinositol 3-Kinases - pharmacology PI3K Plasmids prostate cancer Prostatic Neoplasms - pathology Receptors, Androgen - drug effects Receptors, Androgen - physiology Signal Transduction Tumor Cells, Cultured |
| title | Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells |
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