Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human astrocytic tumors
High‐grade astrocytic tumors, such as glioblastoma, possess rich vascular components, which are necessary for their growth. VEGF‐A is considered to be the major mediator of angiogenesis in malignant neoplasms including high‐grade astrocytic tumors. The upregulation of VEGF‐A expression in tumor cell...
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| Veröffentlicht in: | Neuropathology 2008-12, Vol.28 (6), p.604-611 |
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| creator | Ido, Kazunori Nakagawa, Takao Sakuma, Takahiro Takeuchi, Hiroaki Sato, Kazufumi Kubota, Toshihiko |
| description | High‐grade astrocytic tumors, such as glioblastoma, possess rich vascular components, which are necessary for their growth. VEGF‐A is considered to be the major mediator of angiogenesis in malignant neoplasms including high‐grade astrocytic tumors. The upregulation of VEGF‐A expression in tumor cells is induced by two mechanisms: the transcriptional activation and the post‐transcriptional stabilization of VEGF‐A mRNA. While the former mechanism mediated by hypoxia inducible factor‐1 alpha (HIF‐1α) has been revealed, the latter mediated by mRNA stability factor HuR remains unclear in astrocytic tumors. In the present study, we investigated the expression of VEGF‐A and mRNA stability factor HuR in supratentorial astrocytic tumors of 27 adults using RT‐PCR, ELISA, and immunohistochemistry. Furthermore, we studied the involvement of HuR in the upregulation of VEGF‐A expression using malignant astrocytoma cell lines. In higher‐grade astrocytic tumors, the level of VEGF‐A and microvascular density were elevated, cytoplasmic expression of HuR, which potentially means the protection of VEGF‐A mRNA from degradation by ribonucleases, appeared, and they were correlated positively. In in vitro experiments, the inhibition of the cytoplasmic translocation of HuR protein by leptomycin B (LMB) reduced the upregulation of VEGF‐A expression in malignant astrocytic tumor cells under hypoxic conditions. These findings suggest that the expression of VEGF‐A and cytoplasmic translocation of HuR relates to the histological grade, and that HuR is involved in the upregulation of VEGF‐A expression, in human astrocytic tumors. |
| doi_str_mv | 10.1111/j.1440-1789.2008.00926.x |
| format | Article |
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VEGF‐A is considered to be the major mediator of angiogenesis in malignant neoplasms including high‐grade astrocytic tumors. The upregulation of VEGF‐A expression in tumor cells is induced by two mechanisms: the transcriptional activation and the post‐transcriptional stabilization of VEGF‐A mRNA. While the former mechanism mediated by hypoxia inducible factor‐1 alpha (HIF‐1α) has been revealed, the latter mediated by mRNA stability factor HuR remains unclear in astrocytic tumors. In the present study, we investigated the expression of VEGF‐A and mRNA stability factor HuR in supratentorial astrocytic tumors of 27 adults using RT‐PCR, ELISA, and immunohistochemistry. Furthermore, we studied the involvement of HuR in the upregulation of VEGF‐A expression using malignant astrocytoma cell lines. In higher‐grade astrocytic tumors, the level of VEGF‐A and microvascular density were elevated, cytoplasmic expression of HuR, which potentially means the protection of VEGF‐A mRNA from degradation by ribonucleases, appeared, and they were correlated positively. In in vitro experiments, the inhibition of the cytoplasmic translocation of HuR protein by leptomycin B (LMB) reduced the upregulation of VEGF‐A expression in malignant astrocytic tumor cells under hypoxic conditions. These findings suggest that the expression of VEGF‐A and cytoplasmic translocation of HuR relates to the histological grade, and that HuR is involved in the upregulation of VEGF‐A expression, in human astrocytic tumors.</description><identifier>ISSN: 0919-6544</identifier><identifier>EISSN: 1440-1789</identifier><identifier>DOI: 10.1111/j.1440-1789.2008.00926.x</identifier><identifier>PMID: 18498284</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Adult ; Aged ; Aged, 80 and over ; angiogenesis ; Angiogenesis Inducing Agents ; Antigens, Surface - genetics ; Antigens, Surface - metabolism ; astrocytic tumor ; Astrocytoma - genetics ; Astrocytoma - metabolism ; Astrocytoma - pathology ; Cytoplasm - metabolism ; ELAV Proteins ; ELAV-Like Protein 1 ; Enzyme-Linked Immunosorbent Assay ; Fatty Acids, Unsaturated - pharmacology ; Female ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Humans ; HuR ; hypoxia ; Immunohistochemistry ; Male ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Processing, Post-Transcriptional ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Supratentorial Neoplasms - genetics ; Supratentorial Neoplasms - metabolism ; Supratentorial Neoplasms - pathology ; Tumor Cells, Cultured ; Up-Regulation ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; VEGF-A ; Young Adult</subject><ispartof>Neuropathology, 2008-12, Vol.28 (6), p.604-611</ispartof><rights>2008 Japanese Society of Neuropathology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4606-40af897ade2b6edc26d64f44e6b857919e43f9352456927ccca815e5110755653</citedby><cites>FETCH-LOGICAL-c4606-40af897ade2b6edc26d64f44e6b857919e43f9352456927ccca815e5110755653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1440-1789.2008.00926.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1440-1789.2008.00926.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18498284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ido, Kazunori</creatorcontrib><creatorcontrib>Nakagawa, Takao</creatorcontrib><creatorcontrib>Sakuma, Takahiro</creatorcontrib><creatorcontrib>Takeuchi, Hiroaki</creatorcontrib><creatorcontrib>Sato, Kazufumi</creatorcontrib><creatorcontrib>Kubota, Toshihiko</creatorcontrib><title>Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human astrocytic tumors</title><title>Neuropathology</title><addtitle>Neuropathology</addtitle><description>High‐grade astrocytic tumors, such as glioblastoma, possess rich vascular components, which are necessary for their growth. VEGF‐A is considered to be the major mediator of angiogenesis in malignant neoplasms including high‐grade astrocytic tumors. The upregulation of VEGF‐A expression in tumor cells is induced by two mechanisms: the transcriptional activation and the post‐transcriptional stabilization of VEGF‐A mRNA. While the former mechanism mediated by hypoxia inducible factor‐1 alpha (HIF‐1α) has been revealed, the latter mediated by mRNA stability factor HuR remains unclear in astrocytic tumors. In the present study, we investigated the expression of VEGF‐A and mRNA stability factor HuR in supratentorial astrocytic tumors of 27 adults using RT‐PCR, ELISA, and immunohistochemistry. Furthermore, we studied the involvement of HuR in the upregulation of VEGF‐A expression using malignant astrocytoma cell lines. In higher‐grade astrocytic tumors, the level of VEGF‐A and microvascular density were elevated, cytoplasmic expression of HuR, which potentially means the protection of VEGF‐A mRNA from degradation by ribonucleases, appeared, and they were correlated positively. In in vitro experiments, the inhibition of the cytoplasmic translocation of HuR protein by leptomycin B (LMB) reduced the upregulation of VEGF‐A expression in malignant astrocytic tumor cells under hypoxic conditions. These findings suggest that the expression of VEGF‐A and cytoplasmic translocation of HuR relates to the histological grade, and that HuR is involved in the upregulation of VEGF‐A expression, in human astrocytic tumors.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>angiogenesis</subject><subject>Angiogenesis Inducing Agents</subject><subject>Antigens, Surface - genetics</subject><subject>Antigens, Surface - metabolism</subject><subject>astrocytic tumor</subject><subject>Astrocytoma - genetics</subject><subject>Astrocytoma - metabolism</subject><subject>Astrocytoma - pathology</subject><subject>Cytoplasm - metabolism</subject><subject>ELAV Proteins</subject><subject>ELAV-Like Protein 1</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fatty Acids, Unsaturated - pharmacology</subject><subject>Female</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - pathology</subject><subject>Humans</subject><subject>HuR</subject><subject>hypoxia</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA Processing, Post-Transcriptional</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Supratentorial Neoplasms - genetics</subject><subject>Supratentorial Neoplasms - metabolism</subject><subject>Supratentorial Neoplasms - pathology</subject><subject>Tumor Cells, Cultured</subject><subject>Up-Regulation</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF-A</subject><subject>Young Adult</subject><issn>0919-6544</issn><issn>1440-1789</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uEzEURi0EoqHwCsgrdjPYHv8uWERVaAslrSJaJDaW4_EQpzPjYHva5O2ZkKgsize2dM-5V74fABCjEo_n47rElKICC6lKgpAsEVKEl9sXYPJUeAkmSGFVcEbpCXiT0hohLBSRr8EJllRJIukE3M-2m-hS8qGHoYEPJtmhNRG6vg555VpvWvgrhse8go2xOcRiCk1fw24xn8KUzdK3Pu-ONXgxLKDv4WroTA9NyjHYXfYW5qELMb0FrxrTJvfueJ-C28-z72cXxdX1-eXZ9KqwlCNeUGQaqYSpHVlyV1vCa04bSh1fSibGLzlaNapihDKuiLDWGomZYxgjwRhn1Sn4cOi7ieH34FLWnU_Wta3pXRiS5koxIoR4FsRKEKIwHkF5AG0MKUXX6E30nYk7jZHeJ6LXer94vV-83iei_yait6P6_jhjWHau_iceIxiBTwfg0bdu99-N9Xx2ezO-Rr84-D5lt33yTbzXXFSC6R_zc_3tZv717svPhb6r_gBnVanm</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Ido, Kazunori</creator><creator>Nakagawa, Takao</creator><creator>Sakuma, Takahiro</creator><creator>Takeuchi, Hiroaki</creator><creator>Sato, Kazufumi</creator><creator>Kubota, Toshihiko</creator><general>Blackwell Publishing Asia</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>7TK</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>200812</creationdate><title>Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human astrocytic tumors</title><author>Ido, Kazunori ; Nakagawa, Takao ; Sakuma, Takahiro ; Takeuchi, Hiroaki ; Sato, Kazufumi ; Kubota, Toshihiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4606-40af897ade2b6edc26d64f44e6b857919e43f9352456927ccca815e5110755653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>angiogenesis</topic><topic>Angiogenesis Inducing Agents</topic><topic>Antigens, Surface - genetics</topic><topic>Antigens, Surface - metabolism</topic><topic>astrocytic tumor</topic><topic>Astrocytoma - genetics</topic><topic>Astrocytoma - metabolism</topic><topic>Astrocytoma - pathology</topic><topic>Cytoplasm - metabolism</topic><topic>ELAV Proteins</topic><topic>ELAV-Like Protein 1</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fatty Acids, Unsaturated - pharmacology</topic><topic>Female</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - metabolism</topic><topic>Glioblastoma - pathology</topic><topic>Humans</topic><topic>HuR</topic><topic>hypoxia</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA Processing, Post-Transcriptional</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Supratentorial Neoplasms - genetics</topic><topic>Supratentorial Neoplasms - metabolism</topic><topic>Supratentorial Neoplasms - pathology</topic><topic>Tumor Cells, Cultured</topic><topic>Up-Regulation</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF-A</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ido, Kazunori</creatorcontrib><creatorcontrib>Nakagawa, Takao</creatorcontrib><creatorcontrib>Sakuma, Takahiro</creatorcontrib><creatorcontrib>Takeuchi, Hiroaki</creatorcontrib><creatorcontrib>Sato, Kazufumi</creatorcontrib><creatorcontrib>Kubota, Toshihiko</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>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuropathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ido, Kazunori</au><au>Nakagawa, Takao</au><au>Sakuma, Takahiro</au><au>Takeuchi, Hiroaki</au><au>Sato, Kazufumi</au><au>Kubota, Toshihiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human astrocytic tumors</atitle><jtitle>Neuropathology</jtitle><addtitle>Neuropathology</addtitle><date>2008-12</date><risdate>2008</risdate><volume>28</volume><issue>6</issue><spage>604</spage><epage>611</epage><pages>604-611</pages><issn>0919-6544</issn><eissn>1440-1789</eissn><abstract>High‐grade astrocytic tumors, such as glioblastoma, possess rich vascular components, which are necessary for their growth. VEGF‐A is considered to be the major mediator of angiogenesis in malignant neoplasms including high‐grade astrocytic tumors. The upregulation of VEGF‐A expression in tumor cells is induced by two mechanisms: the transcriptional activation and the post‐transcriptional stabilization of VEGF‐A mRNA. While the former mechanism mediated by hypoxia inducible factor‐1 alpha (HIF‐1α) has been revealed, the latter mediated by mRNA stability factor HuR remains unclear in astrocytic tumors. In the present study, we investigated the expression of VEGF‐A and mRNA stability factor HuR in supratentorial astrocytic tumors of 27 adults using RT‐PCR, ELISA, and immunohistochemistry. Furthermore, we studied the involvement of HuR in the upregulation of VEGF‐A expression using malignant astrocytoma cell lines. In higher‐grade astrocytic tumors, the level of VEGF‐A and microvascular density were elevated, cytoplasmic expression of HuR, which potentially means the protection of VEGF‐A mRNA from degradation by ribonucleases, appeared, and they were correlated positively. In in vitro experiments, the inhibition of the cytoplasmic translocation of HuR protein by leptomycin B (LMB) reduced the upregulation of VEGF‐A expression in malignant astrocytic tumor cells under hypoxic conditions. These findings suggest that the expression of VEGF‐A and cytoplasmic translocation of HuR relates to the histological grade, and that HuR is involved in the upregulation of VEGF‐A expression, in human astrocytic tumors.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>18498284</pmid><doi>10.1111/j.1440-1789.2008.00926.x</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over angiogenesis Angiogenesis Inducing Agents Antigens, Surface - genetics Antigens, Surface - metabolism astrocytic tumor Astrocytoma - genetics Astrocytoma - metabolism Astrocytoma - pathology Cytoplasm - metabolism ELAV Proteins ELAV-Like Protein 1 Enzyme-Linked Immunosorbent Assay Fatty Acids, Unsaturated - pharmacology Female Glioblastoma - genetics Glioblastoma - metabolism Glioblastoma - pathology Humans HuR hypoxia Immunohistochemistry Male Middle Aged Reverse Transcriptase Polymerase Chain Reaction RNA Processing, Post-Transcriptional RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Supratentorial Neoplasms - genetics Supratentorial Neoplasms - metabolism Supratentorial Neoplasms - pathology Tumor Cells, Cultured Up-Regulation Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism VEGF-A Young Adult |
| title | Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human astrocytic tumors |
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