Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer
Background: Activin A is a multi-functional cytokine belonging to the transforming growth factor- β (TGF- β ) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that inhibin β A subunit ( INHBA ) mRNA is overexpressed in gastric cancer (GC) specimens and...
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| creator | Kaneda, H Arao, T Matsumoto, K De Velasco, M A Tamura, D Aomatsu, K Kudo, K Sakai, K Nagai, T Fujita, Y Tanaka, K Yanagihara, K Yamada, Y Okamoto, I Nakagawa, K Nishio, K |
| description | Background:
Activin A is a multi-functional cytokine belonging to the transforming growth factor-
β
(TGF-
β
) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that
inhibin β A subunit
(
INHBA
) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC.
Methods:
Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs)
in vitro
and a stable
INHBA
-introduced GC cell line
in vivo
.
Results:
Compared with TGF-
β
, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable
INHBA
-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis
in vivo
.
Conclusion:
Our findings highlight the suppressive role of activin A, unlike TGF-
β
, on tumour growth and angiogenesis in GC. |
| doi_str_mv | 10.1038/bjc.2011.348 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3208490</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1008826856</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-a7df80903adbb69f3ce68172df9168da5a8945958c23c7468e9a0eb23e5778813</originalsourceid><addsrcrecordid>eNp9ksur1DAUxoMo3nF051qCILqwYx59nGyE4eILLrjRdUjT0zZDJx2Tdi7-96bOOFcFXYXk_PjOd84XQp5ytuFMwpt6ZzeCcb6ROdwjK15IkXEQ1X2yYoxVGVOCXZFHMe7SVTGoHpIrwUFVUokV6bd2ckfn6ZY637vaTZEeTbTzYAJF34xTj4MzA7U4DLQL4-3UU-MbGufDIWCMGOk078c5pNfOjR16jC4mMdqZOAVnqTXeYnhMHrRmiPjkfK7J1_fvvlx_zG4-f_h0vb3JbCHLKTNV00KyKU1T16VqpcUSeCWaVvESGlMYUHmhCrBC2iovAZVhWAuJRVUBcLkmb0-6h7neY2PRT8EM-hDc3oTvejRO_1nxrtfdeNRSMMhT4zV5eRYI47cZ46T3Li7TG4_jHDWo5IflChL56r8kZwxAlFCUCX3-F7pLK_NpEfpnEiDY0vn1CbJhjDFge3HNmV6y1ilrvWStU9YJf_b7pBf4V7gJeHEGUqBmaEMKwsU7Li-Xz5InLjtxMZV8h-HO3D8a0xPvzTQHvAgmaGEW5Ac4Qczw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>897398200</pqid></control><display><type>article</type><title>Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer</title><source>MEDLINE</source><source>Nature</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Kaneda, H ; Arao, T ; Matsumoto, K ; De Velasco, M A ; Tamura, D ; Aomatsu, K ; Kudo, K ; Sakai, K ; Nagai, T ; Fujita, Y ; Tanaka, K ; Yanagihara, K ; Yamada, Y ; Okamoto, I ; Nakagawa, K ; Nishio, K</creator><creatorcontrib>Kaneda, H ; Arao, T ; Matsumoto, K ; De Velasco, M A ; Tamura, D ; Aomatsu, K ; Kudo, K ; Sakai, K ; Nagai, T ; Fujita, Y ; Tanaka, K ; Yanagihara, K ; Yamada, Y ; Okamoto, I ; Nakagawa, K ; Nishio, K</creatorcontrib><description>Background:
Activin A is a multi-functional cytokine belonging to the transforming growth factor-
β
(TGF-
β
) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that
inhibin β A subunit
(
INHBA
) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC.
Methods:
Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs)
in vitro
and a stable
INHBA
-introduced GC cell line
in vivo
.
Results:
Compared with TGF-
β
, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable
INHBA
-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis
in vivo
.
Conclusion:
Our findings highlight the suppressive role of activin A, unlike TGF-
β
, on tumour growth and angiogenesis in GC.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2011.348</identifier><identifier>PMID: 21897392</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/45/612/1243 ; 631/45/776/1174 ; 692/699/67/1504/1829 ; 692/699/67/2328 ; Activins - physiology ; Angiogenesis ; Animals ; Antibodies ; Apoptosis ; Base Sequence ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell growth ; Cell Proliferation ; Cells, Cultured ; Chromatin Immunoprecipitation ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; Cyclin-dependent kinases ; DNA Primers ; Drug Resistance ; Enzyme-Linked Immunosorbent Assay ; Epidemiology ; Female ; Gastric cancer ; Gastroenterology. Liver. Pancreas. Abdomen ; Growth factors ; Humans ; Kinases ; Medical research ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Diagnostics ; Molecular Medicine ; Neovascularization, Pathologic - prevention & control ; Neuroblastoma ; Oncology ; Phosphorylation ; Smad2 Protein - metabolism ; Stem cells ; Stomach Neoplasms - blood supply ; Stomach Neoplasms - pathology ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors ; Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><ispartof>British journal of cancer, 2011-10, Vol.105 (8), p.1210-1217</ispartof><rights>The Author(s) 2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Oct 11, 2011</rights><rights>Copyright © 2011 Cancer Research UK 2011 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-a7df80903adbb69f3ce68172df9168da5a8945958c23c7468e9a0eb23e5778813</citedby><cites>FETCH-LOGICAL-c536t-a7df80903adbb69f3ce68172df9168da5a8945958c23c7468e9a0eb23e5778813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208490/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208490/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,2728,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24615324$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21897392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaneda, H</creatorcontrib><creatorcontrib>Arao, T</creatorcontrib><creatorcontrib>Matsumoto, K</creatorcontrib><creatorcontrib>De Velasco, M A</creatorcontrib><creatorcontrib>Tamura, D</creatorcontrib><creatorcontrib>Aomatsu, K</creatorcontrib><creatorcontrib>Kudo, K</creatorcontrib><creatorcontrib>Sakai, K</creatorcontrib><creatorcontrib>Nagai, T</creatorcontrib><creatorcontrib>Fujita, Y</creatorcontrib><creatorcontrib>Tanaka, K</creatorcontrib><creatorcontrib>Yanagihara, K</creatorcontrib><creatorcontrib>Yamada, Y</creatorcontrib><creatorcontrib>Okamoto, I</creatorcontrib><creatorcontrib>Nakagawa, K</creatorcontrib><creatorcontrib>Nishio, K</creatorcontrib><title>Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Activin A is a multi-functional cytokine belonging to the transforming growth factor-
β
(TGF-
β
) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that
inhibin β A subunit
(
INHBA
) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC.
Methods:
Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs)
in vitro
and a stable
INHBA
-introduced GC cell line
in vivo
.
Results:
Compared with TGF-
β
, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable
INHBA
-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis
in vivo
.
Conclusion:
Our findings highlight the suppressive role of activin A, unlike TGF-
β
, on tumour growth and angiogenesis in GC.</description><subject>631/45/612/1243</subject><subject>631/45/776/1174</subject><subject>692/699/67/1504/1829</subject><subject>692/699/67/2328</subject><subject>Activins - physiology</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Chromatin Immunoprecipitation</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>Cyclin-dependent kinases</subject><subject>DNA Primers</subject><subject>Drug Resistance</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Neovascularization, Pathologic - prevention & control</subject><subject>Neuroblastoma</subject><subject>Oncology</subject><subject>Phosphorylation</subject><subject>Smad2 Protein - metabolism</subject><subject>Stem cells</subject><subject>Stomach Neoplasms - blood supply</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><subject>Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9ksur1DAUxoMo3nF051qCILqwYx59nGyE4eILLrjRdUjT0zZDJx2Tdi7-96bOOFcFXYXk_PjOd84XQp5ytuFMwpt6ZzeCcb6ROdwjK15IkXEQ1X2yYoxVGVOCXZFHMe7SVTGoHpIrwUFVUokV6bd2ckfn6ZY637vaTZEeTbTzYAJF34xTj4MzA7U4DLQL4-3UU-MbGufDIWCMGOk078c5pNfOjR16jC4mMdqZOAVnqTXeYnhMHrRmiPjkfK7J1_fvvlx_zG4-f_h0vb3JbCHLKTNV00KyKU1T16VqpcUSeCWaVvESGlMYUHmhCrBC2iovAZVhWAuJRVUBcLkmb0-6h7neY2PRT8EM-hDc3oTvejRO_1nxrtfdeNRSMMhT4zV5eRYI47cZ46T3Li7TG4_jHDWo5IflChL56r8kZwxAlFCUCX3-F7pLK_NpEfpnEiDY0vn1CbJhjDFge3HNmV6y1ilrvWStU9YJf_b7pBf4V7gJeHEGUqBmaEMKwsU7Li-Xz5InLjtxMZV8h-HO3D8a0xPvzTQHvAgmaGEW5Ac4Qczw</recordid><startdate>20111011</startdate><enddate>20111011</enddate><creator>Kaneda, H</creator><creator>Arao, T</creator><creator>Matsumoto, K</creator><creator>De Velasco, M A</creator><creator>Tamura, D</creator><creator>Aomatsu, K</creator><creator>Kudo, K</creator><creator>Sakai, K</creator><creator>Nagai, T</creator><creator>Fujita, Y</creator><creator>Tanaka, K</creator><creator>Yanagihara, K</creator><creator>Yamada, Y</creator><creator>Okamoto, I</creator><creator>Nakagawa, K</creator><creator>Nishio, K</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20111011</creationdate><title>Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer</title><author>Kaneda, H ; Arao, T ; Matsumoto, K ; De Velasco, M A ; Tamura, D ; Aomatsu, K ; Kudo, K ; Sakai, K ; Nagai, T ; Fujita, Y ; Tanaka, K ; Yanagihara, K ; Yamada, Y ; Okamoto, I ; Nakagawa, K ; Nishio, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-a7df80903adbb69f3ce68172df9168da5a8945958c23c7468e9a0eb23e5778813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/45/612/1243</topic><topic>631/45/776/1174</topic><topic>692/699/67/1504/1829</topic><topic>692/699/67/2328</topic><topic>Activins - physiology</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell growth</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Chromatin Immunoprecipitation</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>Cyclin-dependent kinases</topic><topic>DNA Primers</topic><topic>Drug Resistance</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Kinases</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Neovascularization, Pathologic - prevention & control</topic><topic>Neuroblastoma</topic><topic>Oncology</topic><topic>Phosphorylation</topic><topic>Smad2 Protein - metabolism</topic><topic>Stem cells</topic><topic>Stomach Neoplasms - blood supply</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><topic>Vascular Endothelial Growth Factor A - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaneda, H</creatorcontrib><creatorcontrib>Arao, T</creatorcontrib><creatorcontrib>Matsumoto, K</creatorcontrib><creatorcontrib>De Velasco, M A</creatorcontrib><creatorcontrib>Tamura, D</creatorcontrib><creatorcontrib>Aomatsu, K</creatorcontrib><creatorcontrib>Kudo, K</creatorcontrib><creatorcontrib>Sakai, K</creatorcontrib><creatorcontrib>Nagai, T</creatorcontrib><creatorcontrib>Fujita, Y</creatorcontrib><creatorcontrib>Tanaka, K</creatorcontrib><creatorcontrib>Yanagihara, K</creatorcontrib><creatorcontrib>Yamada, Y</creatorcontrib><creatorcontrib>Okamoto, I</creatorcontrib><creatorcontrib>Nakagawa, K</creatorcontrib><creatorcontrib>Nishio, K</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><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>ProQuest Central (Corporate)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaneda, H</au><au>Arao, T</au><au>Matsumoto, K</au><au>De Velasco, M A</au><au>Tamura, D</au><au>Aomatsu, K</au><au>Kudo, K</au><au>Sakai, K</au><au>Nagai, T</au><au>Fujita, Y</au><au>Tanaka, K</au><au>Yanagihara, K</au><au>Yamada, Y</au><au>Okamoto, I</au><au>Nakagawa, K</au><au>Nishio, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2011-10-11</date><risdate>2011</risdate><volume>105</volume><issue>8</issue><spage>1210</spage><epage>1217</epage><pages>1210-1217</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Activin A is a multi-functional cytokine belonging to the transforming growth factor-
β
(TGF-
β
) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that
inhibin β A subunit
(
INHBA
) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC.
Methods:
Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs)
in vitro
and a stable
INHBA
-introduced GC cell line
in vivo
.
Results:
Compared with TGF-
β
, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable
INHBA
-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis
in vivo
.
Conclusion:
Our findings highlight the suppressive role of activin A, unlike TGF-
β
, on tumour growth and angiogenesis in GC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21897392</pmid><doi>10.1038/bjc.2011.348</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2011-10, Vol.105 (8), p.1210-1217 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3208490 |
| source | MEDLINE; Nature; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 631/45/612/1243 631/45/776/1174 692/699/67/1504/1829 692/699/67/2328 Activins - physiology Angiogenesis Animals Antibodies Apoptosis Base Sequence Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cell growth Cell Proliferation Cells, Cultured Chromatin Immunoprecipitation Cyclin-Dependent Kinase Inhibitor p21 - metabolism Cyclin-dependent kinases DNA Primers Drug Resistance Enzyme-Linked Immunosorbent Assay Epidemiology Female Gastric cancer Gastroenterology. Liver. Pancreas. Abdomen Growth factors Humans Kinases Medical research Medical sciences Mice Mice, Inbred BALB C Mice, Nude Molecular Diagnostics Molecular Medicine Neovascularization, Pathologic - prevention & control Neuroblastoma Oncology Phosphorylation Smad2 Protein - metabolism Stem cells Stomach Neoplasms - blood supply Stomach Neoplasms - pathology Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors Vascular Endothelial Growth Factor A - antagonists & inhibitors |
| title | Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T11%3A33%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activin%20A%20inhibits%20vascular%20endothelial%20cell%20growth%20and%20suppresses%20tumour%20angiogenesis%20in%20gastric%20cancer&rft.jtitle=British%20journal%20of%20cancer&rft.au=Kaneda,%20H&rft.date=2011-10-11&rft.volume=105&rft.issue=8&rft.spage=1210&rft.epage=1217&rft.pages=1210-1217&rft.issn=0007-0920&rft.eissn=1532-1827&rft.coden=BJCAAI&rft_id=info:doi/10.1038/bjc.2011.348&rft_dat=%3Cproquest_pubme%3E1008826856%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=897398200&rft_id=info:pmid/21897392&rfr_iscdi=true |