Androgen Regulation of Parathyroid Hormone-Related Peptide Production in Human Prostate Cancer Cells
PTHrP is the major pathogenetic factor for hypercalcemia in several malignancies including prostate cancer. In the current study, we have assessed the ability of androgens to regulate PTHrP production in androgen-insensitive human prostate cancer cells PC-3 and cells transfected with androgen recept...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2003-03, Vol.144 (3), p.858-867 |
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| creator | Pizzi, Helena Gladu, Julienne Carpio, Luisa Miao, Dengshun Goltzman, David Rabbani, Shafaat A |
| description | PTHrP is the major pathogenetic factor for hypercalcemia in several malignancies including prostate cancer. In the current study, we have assessed the ability of androgens to regulate PTHrP production in androgen-insensitive human prostate cancer cells PC-3 and cells transfected with androgen receptor (PC-3T). Androgen responsiveness caused a marked decrease in PC-3T cell growth, and treatment of these cells with dihydrotestosterone led to inhibition of PTHrP production. These inhibitory effects were readily reversed by androgen receptor antagonist flutamide. To determine the effect of androgens on tumor growth and PTHrP production in vivo, PC-3 and PC-3T cells were injected into the right flank of male BALB/c nu/nu mice. Animals inoculated with PC-3 and PC-3T cells developed palpable tumors at wk 2 and 4, respectively. Inoculation of PC-3T cells into castrated animals resulted in rapid tumor growth in PC-3T tumors, effects that were reversed in PC-3T tumors grown in castrated hosts. Using PTHrP promoter luciferase reporter, a 30% decrease in luciferase activity was seen following treatment with dihydrotestosterone. These results indicate that PC-3 cell growth correlates inversely with androgen sensitivity and directly with PTHrP production in vitro and in vivo, androgens can regulate PTHrP production, and the androgen effect on PTHrP is mediated at least in part by transcriptional regulation via the androgen receptor. |
| doi_str_mv | 10.1210/en.2002-220754 |
| format | Article |
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In the current study, we have assessed the ability of androgens to regulate PTHrP production in androgen-insensitive human prostate cancer cells PC-3 and cells transfected with androgen receptor (PC-3T). Androgen responsiveness caused a marked decrease in PC-3T cell growth, and treatment of these cells with dihydrotestosterone led to inhibition of PTHrP production. These inhibitory effects were readily reversed by androgen receptor antagonist flutamide. To determine the effect of androgens on tumor growth and PTHrP production in vivo, PC-3 and PC-3T cells were injected into the right flank of male BALB/c nu/nu mice. Animals inoculated with PC-3 and PC-3T cells developed palpable tumors at wk 2 and 4, respectively. Inoculation of PC-3T cells into castrated animals resulted in rapid tumor growth in PC-3T tumors, effects that were reversed in PC-3T tumors grown in castrated hosts. Using PTHrP promoter luciferase reporter, a 30% decrease in luciferase activity was seen following treatment with dihydrotestosterone. These results indicate that PC-3 cell growth correlates inversely with androgen sensitivity and directly with PTHrP production in vitro and in vivo, androgens can regulate PTHrP production, and the androgen effect on PTHrP is mediated at least in part by transcriptional regulation via the androgen receptor.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2002-220754</identifier><identifier>PMID: 12586762</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Androgen receptors ; Androgens ; Androgens - physiology ; Animals ; Biological and medical sciences ; Cell Division - drug effects ; Cell growth ; Dihydrotestosterone ; Dihydrotestosterone - pharmacology ; Flutamide ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Expression Regulation - drug effects ; Gene regulation ; Human parathyroid hormone ; Human performance ; Humans ; Hypercalcemia ; Immunohistochemistry ; In vivo methods and tests ; Inoculation ; Male ; Malignancy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Orchiectomy ; Parathyroid hormone ; Parathyroid Hormone-Related Protein ; Peptide Hormones - analysis ; Peptide Hormones - biosynthesis ; Peptide Hormones - genetics ; Promoter Regions, Genetic ; Prostate cancer ; Prostatic Neoplasms - chemistry ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Rats ; Receptors ; Receptors, Androgen - genetics ; Receptors, Androgen - physiology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Transfection ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Endocrinology (Philadelphia), 2003-03, Vol.144 (3), p.858-867</ispartof><rights>Copyright © 2003 by The Endocrine Society 2003</rights><rights>2003 INIST-CNRS</rights><rights>Copyright © 2003 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-4554f0d3eb7872518bfed9a276f9e39a04d3c5cab5099330d531ba2aa594c7163</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14571674$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12586762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pizzi, Helena</creatorcontrib><creatorcontrib>Gladu, Julienne</creatorcontrib><creatorcontrib>Carpio, Luisa</creatorcontrib><creatorcontrib>Miao, Dengshun</creatorcontrib><creatorcontrib>Goltzman, David</creatorcontrib><creatorcontrib>Rabbani, Shafaat A</creatorcontrib><title>Androgen Regulation of Parathyroid Hormone-Related Peptide Production in Human Prostate Cancer Cells</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>PTHrP is the major pathogenetic factor for hypercalcemia in several malignancies including prostate cancer. In the current study, we have assessed the ability of androgens to regulate PTHrP production in androgen-insensitive human prostate cancer cells PC-3 and cells transfected with androgen receptor (PC-3T). Androgen responsiveness caused a marked decrease in PC-3T cell growth, and treatment of these cells with dihydrotestosterone led to inhibition of PTHrP production. These inhibitory effects were readily reversed by androgen receptor antagonist flutamide. To determine the effect of androgens on tumor growth and PTHrP production in vivo, PC-3 and PC-3T cells were injected into the right flank of male BALB/c nu/nu mice. Animals inoculated with PC-3 and PC-3T cells developed palpable tumors at wk 2 and 4, respectively. Inoculation of PC-3T cells into castrated animals resulted in rapid tumor growth in PC-3T tumors, effects that were reversed in PC-3T tumors grown in castrated hosts. Using PTHrP promoter luciferase reporter, a 30% decrease in luciferase activity was seen following treatment with dihydrotestosterone. These results indicate that PC-3 cell growth correlates inversely with androgen sensitivity and directly with PTHrP production in vitro and in vivo, androgens can regulate PTHrP production, and the androgen effect on PTHrP is mediated at least in part by transcriptional regulation via the androgen receptor.</description><subject>Androgen receptors</subject><subject>Androgens</subject><subject>Androgens - physiology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Division - drug effects</subject><subject>Cell growth</subject><subject>Dihydrotestosterone</subject><subject>Dihydrotestosterone - pharmacology</subject><subject>Flutamide</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene regulation</subject><subject>Human parathyroid hormone</subject><subject>Human performance</subject><subject>Humans</subject><subject>Hypercalcemia</subject><subject>Immunohistochemistry</subject><subject>In vivo methods and tests</subject><subject>Inoculation</subject><subject>Male</subject><subject>Malignancy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>Orchiectomy</subject><subject>Parathyroid hormone</subject><subject>Parathyroid Hormone-Related Protein</subject><subject>Peptide Hormones - analysis</subject><subject>Peptide Hormones - biosynthesis</subject><subject>Peptide Hormones - genetics</subject><subject>Promoter Regions, Genetic</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - chemistry</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Rats</subject><subject>Receptors</subject><subject>Receptors, Androgen - genetics</subject><subject>Receptors, Androgen - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1LHDEYh4O06Gq99iiBUsHDbPO5mTnKoq4gdJH2HDLJO3ZkJhmTmYP_fbPO4oLgKSR53vf3gdB3SpaUUfIL_JIRwgrGiJLiCC1oJWShqCJf0IIQygvFmDpBpyk956sQgh-jE8pkuVIrtkDu2rsYnsDjR3iaOjO2wePQ4K2JZvz3GkPr8CbEPngoHiH_g8NbGMbWAd7G4Cb7NtF6vJl643dvacwUXhtvIeI1dF36hr42pktwvj_P0N_bmz_rTfHw--5-ff1QWMnlWAgpRUMch1qVikla1g24yjC1airglSHCcSutqSWpKs6Jk5zWhhkjK2EVXfEzdDnvHWJ4mSCNum-TzQ6MhzAlrThhqiQ78McH8DlM0WdvmlNOJC-pEplazpTNoVKERg-x7U181ZToXfsavN61r-f288DFfu1U9-AO-L7uDPzcAyZZ0zUxl9SmAydkjvGmfDVzYRo-Ey3eReXMgnfBxtbDECGlQ6JPzP4HENKp4A</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>Pizzi, Helena</creator><creator>Gladu, Julienne</creator><creator>Carpio, Luisa</creator><creator>Miao, Dengshun</creator><creator>Goltzman, David</creator><creator>Rabbani, Shafaat A</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20030301</creationdate><title>Androgen Regulation of Parathyroid Hormone-Related Peptide Production in Human Prostate Cancer Cells</title><author>Pizzi, Helena ; Gladu, Julienne ; Carpio, Luisa ; Miao, Dengshun ; Goltzman, David ; Rabbani, Shafaat A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-4554f0d3eb7872518bfed9a276f9e39a04d3c5cab5099330d531ba2aa594c7163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Androgen receptors</topic><topic>Androgens</topic><topic>Androgens - physiology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Division - drug effects</topic><topic>Cell growth</topic><topic>Dihydrotestosterone</topic><topic>Dihydrotestosterone - pharmacology</topic><topic>Flutamide</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene regulation</topic><topic>Human parathyroid hormone</topic><topic>Human performance</topic><topic>Humans</topic><topic>Hypercalcemia</topic><topic>Immunohistochemistry</topic><topic>In vivo methods and tests</topic><topic>Inoculation</topic><topic>Male</topic><topic>Malignancy</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasm Transplantation</topic><topic>Orchiectomy</topic><topic>Parathyroid hormone</topic><topic>Parathyroid Hormone-Related Protein</topic><topic>Peptide Hormones - analysis</topic><topic>Peptide Hormones - biosynthesis</topic><topic>Peptide Hormones - genetics</topic><topic>Promoter Regions, Genetic</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - chemistry</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Rats</topic><topic>Receptors</topic><topic>Receptors, Androgen - genetics</topic><topic>Receptors, Androgen - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pizzi, Helena</creatorcontrib><creatorcontrib>Gladu, Julienne</creatorcontrib><creatorcontrib>Carpio, Luisa</creatorcontrib><creatorcontrib>Miao, Dengshun</creatorcontrib><creatorcontrib>Goltzman, David</creatorcontrib><creatorcontrib>Rabbani, Shafaat A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pizzi, Helena</au><au>Gladu, Julienne</au><au>Carpio, Luisa</au><au>Miao, Dengshun</au><au>Goltzman, David</au><au>Rabbani, Shafaat A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Androgen Regulation of Parathyroid Hormone-Related Peptide Production in Human Prostate Cancer Cells</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2003-03-01</date><risdate>2003</risdate><volume>144</volume><issue>3</issue><spage>858</spage><epage>867</epage><pages>858-867</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>PTHrP is the major pathogenetic factor for hypercalcemia in several malignancies including prostate cancer. In the current study, we have assessed the ability of androgens to regulate PTHrP production in androgen-insensitive human prostate cancer cells PC-3 and cells transfected with androgen receptor (PC-3T). Androgen responsiveness caused a marked decrease in PC-3T cell growth, and treatment of these cells with dihydrotestosterone led to inhibition of PTHrP production. These inhibitory effects were readily reversed by androgen receptor antagonist flutamide. To determine the effect of androgens on tumor growth and PTHrP production in vivo, PC-3 and PC-3T cells were injected into the right flank of male BALB/c nu/nu mice. Animals inoculated with PC-3 and PC-3T cells developed palpable tumors at wk 2 and 4, respectively. Inoculation of PC-3T cells into castrated animals resulted in rapid tumor growth in PC-3T tumors, effects that were reversed in PC-3T tumors grown in castrated hosts. Using PTHrP promoter luciferase reporter, a 30% decrease in luciferase activity was seen following treatment with dihydrotestosterone. These results indicate that PC-3 cell growth correlates inversely with androgen sensitivity and directly with PTHrP production in vitro and in vivo, androgens can regulate PTHrP production, and the androgen effect on PTHrP is mediated at least in part by transcriptional regulation via the androgen receptor.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>12586762</pmid><doi>10.1210/en.2002-220754</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Androgen receptors Androgens Androgens - physiology Animals Biological and medical sciences Cell Division - drug effects Cell growth Dihydrotestosterone Dihydrotestosterone - pharmacology Flutamide Fundamental and applied biological sciences. Psychology Gene Expression Gene Expression Regulation - drug effects Gene regulation Human parathyroid hormone Human performance Humans Hypercalcemia Immunohistochemistry In vivo methods and tests Inoculation Male Malignancy Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Orchiectomy Parathyroid hormone Parathyroid Hormone-Related Protein Peptide Hormones - analysis Peptide Hormones - biosynthesis Peptide Hormones - genetics Promoter Regions, Genetic Prostate cancer Prostatic Neoplasms - chemistry Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Rats Receptors Receptors, Androgen - genetics Receptors, Androgen - physiology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Transfection Tumor Cells, Cultured Tumors |
| title | Androgen Regulation of Parathyroid Hormone-Related Peptide Production in Human Prostate Cancer Cells |
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