Hammerhead Ribozyme-Mediated Cleavage of the Human Insulin-Like Growth Factor-II Ribonucleic Acid in Vitro and in Prostate Cancer Cells
Abstract Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cance...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 1999-05, Vol.140 (5), p.2134-2144 |
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| creator | Xu, Zhao-Dong Oey, Lily Mohan, Subburaman Kawachi, Mark H. Lee, Nan-Sook Rossi, John J. Fujita-Yamaguchi, Yoko |
| description | Abstract
Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cancer cell growth, hammerhead ribozymes targeted to human IGF-II RNA were constructed. Single (R)- and double (RR)-ribozymes were catalytically active in vitro whereas mutant ribozymes (M or MM) did not cleave IGF-II RNA. RR was more active than R. In human prostate cancer PC-3 cells, both R and RR similarly suppressed IGF-II messenger RNA (mRNA) levels (∼40%) compared with the level in parental or M-expressing PC-3 cells. Polymerase II and III promoter-driven R similarly suppressed IGF-II mRNA levels. Suppression of IGF-II mRNA levels by R was associated with suppression of IGF-II protein levels. R- (or RR-) expressing PC-3 cells did not grow under serum-starved conditions and showed prolonged doubling times in the presence of 10% FCS compared with those of parental or M-expressing cells. These results substantiated that IGF-II plays a critical role in prostate cancer cell growth. |
| doi_str_mv | 10.1210/endo.140.5.6687 |
| format | Article |
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Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cancer cell growth, hammerhead ribozymes targeted to human IGF-II RNA were constructed. Single (R)- and double (RR)-ribozymes were catalytically active in vitro whereas mutant ribozymes (M or MM) did not cleave IGF-II RNA. RR was more active than R. In human prostate cancer PC-3 cells, both R and RR similarly suppressed IGF-II messenger RNA (mRNA) levels (∼40%) compared with the level in parental or M-expressing PC-3 cells. Polymerase II and III promoter-driven R similarly suppressed IGF-II mRNA levels. Suppression of IGF-II mRNA levels by R was associated with suppression of IGF-II protein levels. R- (or RR-) expressing PC-3 cells did not grow under serum-starved conditions and showed prolonged doubling times in the presence of 10% FCS compared with those of parental or M-expressing cells. These results substantiated that IGF-II plays a critical role in prostate cancer cell growth.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/endo.140.5.6687</identifier><identifier>PMID: 10218964</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Autocrine signalling ; Base Sequence ; Catalysis ; Cell Division ; Cell growth ; Fetuses ; Gene Expression ; Growth factors ; Humans ; Insulin ; Insulin-like growth factor II ; Insulin-Like Growth Factor II - genetics ; Insulin-like growth factors ; Kinetics ; Male ; Mitogens ; Molecular Sequence Data ; mRNA ; Nucleic Acid Conformation ; Paracrine signalling ; Promoter Regions, Genetic ; Prostate cancer ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Ribonucleic acid ; Ribozymes ; RNA ; RNA - metabolism ; RNA Polymerase III - genetics ; RNA, Catalytic - chemistry ; RNA, Catalytic - metabolism ; RNA, Messenger - metabolism ; Structure-Activity Relationship ; Tumor Cells, Cultured</subject><ispartof>Endocrinology (Philadelphia), 1999-05, Vol.140 (5), p.2134-2144</ispartof><rights>Copyright © 1999 by The Endocrine Society 1999</rights><rights>Copyright © 1999 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3127-95432f70e869934ecdea576513ee06c57227a8c35632b065e7fa4b48daa9a4a3</citedby><cites>FETCH-LOGICAL-c3127-95432f70e869934ecdea576513ee06c57227a8c35632b065e7fa4b48daa9a4a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10218964$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Zhao-Dong</creatorcontrib><creatorcontrib>Oey, Lily</creatorcontrib><creatorcontrib>Mohan, Subburaman</creatorcontrib><creatorcontrib>Kawachi, Mark H.</creatorcontrib><creatorcontrib>Lee, Nan-Sook</creatorcontrib><creatorcontrib>Rossi, John J.</creatorcontrib><creatorcontrib>Fujita-Yamaguchi, Yoko</creatorcontrib><title>Hammerhead Ribozyme-Mediated Cleavage of the Human Insulin-Like Growth Factor-II Ribonucleic Acid in Vitro and in Prostate Cancer Cells</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Abstract
Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cancer cell growth, hammerhead ribozymes targeted to human IGF-II RNA were constructed. Single (R)- and double (RR)-ribozymes were catalytically active in vitro whereas mutant ribozymes (M or MM) did not cleave IGF-II RNA. RR was more active than R. In human prostate cancer PC-3 cells, both R and RR similarly suppressed IGF-II messenger RNA (mRNA) levels (∼40%) compared with the level in parental or M-expressing PC-3 cells. Polymerase II and III promoter-driven R similarly suppressed IGF-II mRNA levels. Suppression of IGF-II mRNA levels by R was associated with suppression of IGF-II protein levels. R- (or RR-) expressing PC-3 cells did not grow under serum-starved conditions and showed prolonged doubling times in the presence of 10% FCS compared with those of parental or M-expressing cells. These results substantiated that IGF-II plays a critical role in prostate cancer cell growth.</description><subject>Autocrine signalling</subject><subject>Base Sequence</subject><subject>Catalysis</subject><subject>Cell Division</subject><subject>Cell growth</subject><subject>Fetuses</subject><subject>Gene Expression</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-Like Growth Factor II - genetics</subject><subject>Insulin-like growth factors</subject><subject>Kinetics</subject><subject>Male</subject><subject>Mitogens</subject><subject>Molecular Sequence Data</subject><subject>mRNA</subject><subject>Nucleic Acid Conformation</subject><subject>Paracrine signalling</subject><subject>Promoter Regions, Genetic</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Ribonucleic acid</subject><subject>Ribozymes</subject><subject>RNA</subject><subject>RNA - metabolism</subject><subject>RNA Polymerase III - genetics</subject><subject>RNA, Catalytic - chemistry</subject><subject>RNA, Catalytic - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>Tumor Cells, Cultured</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2LFDEQhoMo7rh69iYBwYPQs0nna_q4NO7OwIgii9dQk652snYnY9K9sv4B_7aZnT2IF09FwVMvb_EQ8pqzJa85u8DQxSWXbKmWWq_ME7LgjVSV4YY9JQvGuKhMXZsz8iLn27JKKcVzcsZZzVeNlgvyew3jiGmP0NEvfhd_3Y9YfcTOw4QdbQeEO_iGNPZ02iNdzyMEugl5Hnyotv470usUf057egVuiqnabB5SwuwG9I5eOt9RH-hXP6VIITwsn1PMU4mnLQSHibY4DPkledbDkPHV4zwnN1cfbtp1tf10vWkvt5UTvDZVo6Soe8NwpZtGSHQdgjJacYHItFPHZ2HlhNKi3jGt0PQgd3LVATQgQZyTd6fYQ4o_ZsyTHX12pQAEjHO2ujFcS8EK-PYf8DbOKZRqVnDBFGOlSaEuTpQrP-WEvT0kP0K6t5zZoyB7FGSLIKvsUVC5ePOYO-9G7P7iT0YK8P4ExPnw37Q_kiGY-g</recordid><startdate>199905</startdate><enddate>199905</enddate><creator>Xu, Zhao-Dong</creator><creator>Oey, Lily</creator><creator>Mohan, Subburaman</creator><creator>Kawachi, Mark H.</creator><creator>Lee, Nan-Sook</creator><creator>Rossi, John J.</creator><creator>Fujita-Yamaguchi, Yoko</creator><general>Oxford University Press</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>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>199905</creationdate><title>Hammerhead Ribozyme-Mediated Cleavage of the Human Insulin-Like Growth Factor-II Ribonucleic Acid in Vitro and in Prostate Cancer Cells</title><author>Xu, Zhao-Dong ; Oey, Lily ; Mohan, Subburaman ; Kawachi, Mark H. ; Lee, Nan-Sook ; Rossi, John J. ; Fujita-Yamaguchi, Yoko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3127-95432f70e869934ecdea576513ee06c57227a8c35632b065e7fa4b48daa9a4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Autocrine signalling</topic><topic>Base Sequence</topic><topic>Catalysis</topic><topic>Cell Division</topic><topic>Cell growth</topic><topic>Fetuses</topic><topic>Gene Expression</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Insulin</topic><topic>Insulin-like growth factor II</topic><topic>Insulin-Like Growth Factor II - genetics</topic><topic>Insulin-like growth factors</topic><topic>Kinetics</topic><topic>Male</topic><topic>Mitogens</topic><topic>Molecular Sequence Data</topic><topic>mRNA</topic><topic>Nucleic Acid Conformation</topic><topic>Paracrine signalling</topic><topic>Promoter Regions, Genetic</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Ribonucleic acid</topic><topic>Ribozymes</topic><topic>RNA</topic><topic>RNA - metabolism</topic><topic>RNA Polymerase III - genetics</topic><topic>RNA, Catalytic - chemistry</topic><topic>RNA, Catalytic - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Zhao-Dong</creatorcontrib><creatorcontrib>Oey, Lily</creatorcontrib><creatorcontrib>Mohan, Subburaman</creatorcontrib><creatorcontrib>Kawachi, Mark H.</creatorcontrib><creatorcontrib>Lee, Nan-Sook</creatorcontrib><creatorcontrib>Rossi, John J.</creatorcontrib><creatorcontrib>Fujita-Yamaguchi, Yoko</creatorcontrib><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>Xu, Zhao-Dong</au><au>Oey, Lily</au><au>Mohan, Subburaman</au><au>Kawachi, Mark H.</au><au>Lee, Nan-Sook</au><au>Rossi, John J.</au><au>Fujita-Yamaguchi, Yoko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hammerhead Ribozyme-Mediated Cleavage of the Human Insulin-Like Growth Factor-II Ribonucleic Acid in Vitro and in Prostate Cancer Cells</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>1999-05</date><risdate>1999</risdate><volume>140</volume><issue>5</issue><spage>2134</spage><epage>2144</epage><pages>2134-2144</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>Abstract
Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cancer cell growth, hammerhead ribozymes targeted to human IGF-II RNA were constructed. Single (R)- and double (RR)-ribozymes were catalytically active in vitro whereas mutant ribozymes (M or MM) did not cleave IGF-II RNA. RR was more active than R. In human prostate cancer PC-3 cells, both R and RR similarly suppressed IGF-II messenger RNA (mRNA) levels (∼40%) compared with the level in parental or M-expressing PC-3 cells. Polymerase II and III promoter-driven R similarly suppressed IGF-II mRNA levels. Suppression of IGF-II mRNA levels by R was associated with suppression of IGF-II protein levels. R- (or RR-) expressing PC-3 cells did not grow under serum-starved conditions and showed prolonged doubling times in the presence of 10% FCS compared with those of parental or M-expressing cells. These results substantiated that IGF-II plays a critical role in prostate cancer cell growth.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>10218964</pmid><doi>10.1210/endo.140.5.6687</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Endocrinology (Philadelphia), 1999-05, Vol.140 (5), p.2134-2144 |
| issn | 0013-7227 1945-7170 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Autocrine signalling Base Sequence Catalysis Cell Division Cell growth Fetuses Gene Expression Growth factors Humans Insulin Insulin-like growth factor II Insulin-Like Growth Factor II - genetics Insulin-like growth factors Kinetics Male Mitogens Molecular Sequence Data mRNA Nucleic Acid Conformation Paracrine signalling Promoter Regions, Genetic Prostate cancer Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Ribonucleic acid Ribozymes RNA RNA - metabolism RNA Polymerase III - genetics RNA, Catalytic - chemistry RNA, Catalytic - metabolism RNA, Messenger - metabolism Structure-Activity Relationship Tumor Cells, Cultured |
| title | Hammerhead Ribozyme-Mediated Cleavage of the Human Insulin-Like Growth Factor-II Ribonucleic Acid in Vitro and in Prostate Cancer Cells |
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