Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo
This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous “take rate” in NOD-SCID mice, and increased production of PSA. Tumors e...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2006-07, Vol.345 (3), p.1207-1214 |
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| creator | Perryman, L.A. Blair, J.M. Kingsley, E.A. Szymanska, B. Ow, K.T. Wen, V.W. MacKenzie, K.L. Vermeulen, P.B. Jackson, P. Russell, P.J. |
| description | This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous “take rate” in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation. |
| doi_str_mv | 10.1016/j.bbrc.2006.05.020 |
| format | Article |
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Mutant p53 proteins were associated with an increased subcutaneous “take rate” in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2006.05.020</identifier><identifier>PMID: 16723121</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Angiogenesis ; ANOXIA ; APOPTOSIS ; BONE MARROW ; CARCINOMAS ; Cell Line, Tumor ; CELL PROLIFERATION ; Culture Media, Conditioned - pharmacology ; Endostatin ; Endothelium, Vascular - cytology ; Genes, p53 ; Humans ; Hypoxia ; IN VIVO ; Male ; MICE ; MUTANTS ; MUTATIONS ; NECROSIS ; Neoplasms - pathology ; Neovascularization, Pathologic ; p53 ; Proliferation ; PROSTATE ; Prostate cancer ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; PROTEINS ; TUMOR CELLS ; Tumor Suppressor Protein p53 - metabolism ; Umbilical Veins - cytology ; VEGF ; VEINS ; Xenografts</subject><ispartof>Biochemical and biophysical research communications, 2006-07, Vol.345 (3), p.1207-1214</ispartof><rights>2006 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-a7e16d6d9f4d8faf71f999042b9d813a03c5e0bc42b186d1df7d3e46ac130e0f3</citedby><cites>FETCH-LOGICAL-c413t-a7e16d6d9f4d8faf71f999042b9d813a03c5e0bc42b186d1df7d3e46ac130e0f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2006.05.020$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16723121$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/20854344$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Perryman, L.A.</creatorcontrib><creatorcontrib>Blair, J.M.</creatorcontrib><creatorcontrib>Kingsley, E.A.</creatorcontrib><creatorcontrib>Szymanska, B.</creatorcontrib><creatorcontrib>Ow, K.T.</creatorcontrib><creatorcontrib>Wen, V.W.</creatorcontrib><creatorcontrib>MacKenzie, K.L.</creatorcontrib><creatorcontrib>Vermeulen, P.B.</creatorcontrib><creatorcontrib>Jackson, P.</creatorcontrib><creatorcontrib>Russell, P.J.</creatorcontrib><title>Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous “take rate” in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Angiogenesis</subject><subject>ANOXIA</subject><subject>APOPTOSIS</subject><subject>BONE MARROW</subject><subject>CARCINOMAS</subject><subject>Cell Line, Tumor</subject><subject>CELL PROLIFERATION</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Endostatin</subject><subject>Endothelium, Vascular - cytology</subject><subject>Genes, p53</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>IN VIVO</subject><subject>Male</subject><subject>MICE</subject><subject>MUTANTS</subject><subject>MUTATIONS</subject><subject>NECROSIS</subject><subject>Neoplasms - pathology</subject><subject>Neovascularization, Pathologic</subject><subject>p53</subject><subject>Proliferation</subject><subject>PROSTATE</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>PROTEINS</subject><subject>TUMOR CELLS</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Umbilical Veins - cytology</subject><subject>VEGF</subject><subject>VEINS</subject><subject>Xenografts</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-LFDEQxYMo7uzqF_AgAcFb91Yl_Re8yKCrMOx6UBAvIZ1Uz2aY7oxJetz99nY7A970UAQqv_fg1WPsFUKOgNX1Lu-6YHIBUOVQ5iDgCVshtJAJhOIpW8H8k4kWv1-wyxh3AIhF1T5nF1jVQqLAFftxd6SQ0cMhUIzOj9z3_FBKPkxJjylyN_LN7Vp_4Yb2-8j1PlGIPE2DD3wb_K90z_Vo59k6v6WRovujObqjf8Ge9Xof6eX5vWLfPn74uv6Ube5uPq_fbzJToEyZrgkrW9m2L2zT677Gvm1bKETX2galBmlKgs7MC2wqi7avraSi0gYlEPTyir05-fqYnIrGJTL3xo8jmaQENGUhi2Km3p6oQ_A_J4pJDS4uofRIfoqqakA0ZY3_BbEWKCUsjuIEmuBjDNSrQ3CDDo8KQS0FqZ1aClJLQQpKNRc0i16f3aduIPtXcm5kBt6dAJpPdnQUlkQ0GrIuLIGsd__y_w0xLKDP</recordid><startdate>20060707</startdate><enddate>20060707</enddate><creator>Perryman, L.A.</creator><creator>Blair, J.M.</creator><creator>Kingsley, E.A.</creator><creator>Szymanska, B.</creator><creator>Ow, K.T.</creator><creator>Wen, V.W.</creator><creator>MacKenzie, K.L.</creator><creator>Vermeulen, P.B.</creator><creator>Jackson, P.</creator><creator>Russell, P.J.</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20060707</creationdate><title>Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo</title><author>Perryman, L.A. ; Blair, J.M. ; Kingsley, E.A. ; Szymanska, B. ; Ow, K.T. ; Wen, V.W. ; MacKenzie, K.L. ; Vermeulen, P.B. ; Jackson, P. ; Russell, P.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-a7e16d6d9f4d8faf71f999042b9d813a03c5e0bc42b186d1df7d3e46ac130e0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Angiogenesis</topic><topic>ANOXIA</topic><topic>APOPTOSIS</topic><topic>BONE MARROW</topic><topic>CARCINOMAS</topic><topic>Cell Line, Tumor</topic><topic>CELL PROLIFERATION</topic><topic>Culture Media, Conditioned - pharmacology</topic><topic>Endostatin</topic><topic>Endothelium, Vascular - cytology</topic><topic>Genes, p53</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>IN VIVO</topic><topic>Male</topic><topic>MICE</topic><topic>MUTANTS</topic><topic>MUTATIONS</topic><topic>NECROSIS</topic><topic>Neoplasms - pathology</topic><topic>Neovascularization, Pathologic</topic><topic>p53</topic><topic>Proliferation</topic><topic>PROSTATE</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>PROTEINS</topic><topic>TUMOR CELLS</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Umbilical Veins - cytology</topic><topic>VEGF</topic><topic>VEINS</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perryman, L.A.</creatorcontrib><creatorcontrib>Blair, J.M.</creatorcontrib><creatorcontrib>Kingsley, E.A.</creatorcontrib><creatorcontrib>Szymanska, B.</creatorcontrib><creatorcontrib>Ow, K.T.</creatorcontrib><creatorcontrib>Wen, V.W.</creatorcontrib><creatorcontrib>MacKenzie, K.L.</creatorcontrib><creatorcontrib>Vermeulen, P.B.</creatorcontrib><creatorcontrib>Jackson, P.</creatorcontrib><creatorcontrib>Russell, P.J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perryman, L.A.</au><au>Blair, J.M.</au><au>Kingsley, E.A.</au><au>Szymanska, B.</au><au>Ow, K.T.</au><au>Wen, V.W.</au><au>MacKenzie, K.L.</au><au>Vermeulen, P.B.</au><au>Jackson, P.</au><au>Russell, P.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2006-07-07</date><risdate>2006</risdate><volume>345</volume><issue>3</issue><spage>1207</spage><epage>1214</epage><pages>1207-1214</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous “take rate” in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16723121</pmid><doi>10.1016/j.bbrc.2006.05.020</doi><tpages>8</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES Angiogenesis ANOXIA APOPTOSIS BONE MARROW CARCINOMAS Cell Line, Tumor CELL PROLIFERATION Culture Media, Conditioned - pharmacology Endostatin Endothelium, Vascular - cytology Genes, p53 Humans Hypoxia IN VIVO Male MICE MUTANTS MUTATIONS NECROSIS Neoplasms - pathology Neovascularization, Pathologic p53 Proliferation PROSTATE Prostate cancer Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology PROTEINS TUMOR CELLS Tumor Suppressor Protein p53 - metabolism Umbilical Veins - cytology VEGF VEINS Xenografts |
| title | Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo |
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