Estrogen regulates forkhead transcription factor 2 to promote apoptosis of human ovarian granulosa-like tumor cells
•FOXL2 is highly expressed in KGN cells and GCT tissues.•FOXL2 inhibits E2 synthesis, while E2 up-regulated the FOXL2 expression in KGN•cells.•Estrogen induces FOXL2 phosphorylation via GPCR-PKC non-genomic pathway.•Estrogen promotes cell apoptosis via FOXL2. Granulosa cell tumors of the ovary (GCTs...
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| Veröffentlicht in: | The Journal of steroid biochemistry and molecular biology 2019-11, Vol.194, p.105418-105418, Article 105418 |
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| creator | Wu, Jun Miao, Chunlei Lv, Xiaoyu Zhang, Yujie Li, Yanyan Wang, Di |
| description | •FOXL2 is highly expressed in KGN cells and GCT tissues.•FOXL2 inhibits E2 synthesis, while E2 up-regulated the FOXL2 expression in KGN•cells.•Estrogen induces FOXL2 phosphorylation via GPCR-PKC non-genomic pathway.•Estrogen promotes cell apoptosis via FOXL2.
Granulosa cell tumors of the ovary (GCTs) are the predominant form of ovarian stromal tumors and can lead to abnormally secreted estrogen hormones. Studies have reported that forkhead transcription factor 2 (FOXL2) inhibits estrogen synthesis and its gene mutation can lead to GCTs. We unexpected found that estrogen also regulates the expression level of FOXL2. High-dose estrogen increased the expression of FOXL2 in ovarian-like granulosa (KGN) cells at both the mRNA and protein levels. However, no research has reported on the molecular regulatory mechanism and function between estrogen and FOXL2 in the development of GCTs. In this research, FOXL2 was highly expressed in KGN cells and ovarian stromal tumor tissues. Deletion of FOXL2 increased the estrogen secretion in KGN cells. In turn, high-dose estrogen increased the FOXL2 expression levels. FOXL2 was phosphorylated by GPR30 (G protein coupled receptor)-Protein kinase C (PKC) signaling pathway upon estrogen stimulation. Estrogen inhibited cell migration and proliferation, while promoting cell apoptosis. Deletion of FOXL2 inhibited the influence of estrogen on cell proliferation, migration, and apoptosis. Results suggest that estrogen via regulating FOXL2 suppresses cell proliferation and induces cell apoptosis. |
| doi_str_mv | 10.1016/j.jsbmb.2019.105418 |
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Granulosa cell tumors of the ovary (GCTs) are the predominant form of ovarian stromal tumors and can lead to abnormally secreted estrogen hormones. Studies have reported that forkhead transcription factor 2 (FOXL2) inhibits estrogen synthesis and its gene mutation can lead to GCTs. We unexpected found that estrogen also regulates the expression level of FOXL2. High-dose estrogen increased the expression of FOXL2 in ovarian-like granulosa (KGN) cells at both the mRNA and protein levels. However, no research has reported on the molecular regulatory mechanism and function between estrogen and FOXL2 in the development of GCTs. In this research, FOXL2 was highly expressed in KGN cells and ovarian stromal tumor tissues. Deletion of FOXL2 increased the estrogen secretion in KGN cells. In turn, high-dose estrogen increased the FOXL2 expression levels. FOXL2 was phosphorylated by GPR30 (G protein coupled receptor)-Protein kinase C (PKC) signaling pathway upon estrogen stimulation. Estrogen inhibited cell migration and proliferation, while promoting cell apoptosis. Deletion of FOXL2 inhibited the influence of estrogen on cell proliferation, migration, and apoptosis. Results suggest that estrogen via regulating FOXL2 suppresses cell proliferation and induces cell apoptosis.</description><identifier>ISSN: 0960-0760</identifier><identifier>EISSN: 1879-1220</identifier><identifier>DOI: 10.1016/j.jsbmb.2019.105418</identifier><identifier>PMID: 31376461</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Apoptosis ; Apoptosis - drug effects ; Cell adhesion & migration ; Cell growth ; Cell Line ; Cell migration ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Clonal deletion ; Estradiol - pharmacology ; Estrogen ; Estrogens ; Estrogens - pharmacology ; Female ; Forkhead Box Protein L2 - genetics ; Forkhead Box Protein L2 - metabolism ; Forkhead protein ; FOXL2 ; GCTs ; GPR30 ; Granulosa Cell Tumor - metabolism ; Humans ; Kinases ; Middle Aged ; Ovarian cancer ; Ovarian Neoplasms - metabolism ; Point mutation ; Protein kinase C ; Proteins ; RNA, Messenger - metabolism ; Signal transduction ; Transcription factors ; Tumor cells ; Tumors ; Young Adult</subject><ispartof>The Journal of steroid biochemistry and molecular biology, 2019-11, Vol.194, p.105418-105418, Article 105418</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Nov 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-e7611de7ad88f542899f1f78a10697c17a1fb2efdb2f111c5cee22e01d19c2b93</citedby><cites>FETCH-LOGICAL-c387t-e7611de7ad88f542899f1f78a10697c17a1fb2efdb2f111c5cee22e01d19c2b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960076018307660$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31376461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Jun</creatorcontrib><creatorcontrib>Miao, Chunlei</creatorcontrib><creatorcontrib>Lv, Xiaoyu</creatorcontrib><creatorcontrib>Zhang, Yujie</creatorcontrib><creatorcontrib>Li, Yanyan</creatorcontrib><creatorcontrib>Wang, Di</creatorcontrib><title>Estrogen regulates forkhead transcription factor 2 to promote apoptosis of human ovarian granulosa-like tumor cells</title><title>The Journal of steroid biochemistry and molecular biology</title><addtitle>J Steroid Biochem Mol Biol</addtitle><description>•FOXL2 is highly expressed in KGN cells and GCT tissues.•FOXL2 inhibits E2 synthesis, while E2 up-regulated the FOXL2 expression in KGN•cells.•Estrogen induces FOXL2 phosphorylation via GPCR-PKC non-genomic pathway.•Estrogen promotes cell apoptosis via FOXL2.
Granulosa cell tumors of the ovary (GCTs) are the predominant form of ovarian stromal tumors and can lead to abnormally secreted estrogen hormones. Studies have reported that forkhead transcription factor 2 (FOXL2) inhibits estrogen synthesis and its gene mutation can lead to GCTs. We unexpected found that estrogen also regulates the expression level of FOXL2. High-dose estrogen increased the expression of FOXL2 in ovarian-like granulosa (KGN) cells at both the mRNA and protein levels. However, no research has reported on the molecular regulatory mechanism and function between estrogen and FOXL2 in the development of GCTs. In this research, FOXL2 was highly expressed in KGN cells and ovarian stromal tumor tissues. Deletion of FOXL2 increased the estrogen secretion in KGN cells. In turn, high-dose estrogen increased the FOXL2 expression levels. FOXL2 was phosphorylated by GPR30 (G protein coupled receptor)-Protein kinase C (PKC) signaling pathway upon estrogen stimulation. Estrogen inhibited cell migration and proliferation, while promoting cell apoptosis. Deletion of FOXL2 inhibited the influence of estrogen on cell proliferation, migration, and apoptosis. Results suggest that estrogen via regulating FOXL2 suppresses cell proliferation and induces cell apoptosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Clonal deletion</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen</subject><subject>Estrogens</subject><subject>Estrogens - pharmacology</subject><subject>Female</subject><subject>Forkhead Box Protein L2 - genetics</subject><subject>Forkhead Box Protein L2 - metabolism</subject><subject>Forkhead protein</subject><subject>FOXL2</subject><subject>GCTs</subject><subject>GPR30</subject><subject>Granulosa Cell Tumor - metabolism</subject><subject>Humans</subject><subject>Kinases</subject><subject>Middle Aged</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Point mutation</subject><subject>Protein kinase C</subject><subject>Proteins</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal transduction</subject><subject>Transcription factors</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0960-0760</issn><issn>1879-1220</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS0EokvhEyAhS1x6ydZj78bJgQOqyh-pUi9wthxnvHWaxMHjVOq3r5ctHDhwGmn0e2-e5jH2HsQWBNSXw3agbuq2UkBbNvsdNC_YBhrdViCleMk2oq1FJXQtztgbokEIoRTo1-xMgdL1roYNo2vKKR5w5gkP62gzEvcx3d-h7XlOdiaXwpJDnLm3LsfEJc-RLylOMSO3S1xypEA8en63Tnbm8cGmUOahiNcxkq3GcI88r1MROxxHesteeTsSvnue5-znl-sfV9-qm9uv368-31RONTpXqGuAHrXtm8bvd7JpWw9eNxZE3WoH2oLvJPq-kx4A3N4hSokCemid7Fp1zi5OviXtrxUpmynQMYGdMa5kpKwbJfatkAX9-A86xDXNJZ2RqnC78q6joTpRLkWihN4sKUw2PRoQ5tiJGczvTsyxE3PqpKg-PHuv3YT9X82fEgrw6QRgecZDwGTIBZwd9iGhy6aP4b8HngAj_J-9</recordid><startdate>201911</startdate><enddate>201911</enddate><creator>Wu, Jun</creator><creator>Miao, Chunlei</creator><creator>Lv, Xiaoyu</creator><creator>Zhang, Yujie</creator><creator>Li, Yanyan</creator><creator>Wang, Di</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201911</creationdate><title>Estrogen regulates forkhead transcription factor 2 to promote apoptosis of human ovarian granulosa-like tumor cells</title><author>Wu, Jun ; Miao, Chunlei ; Lv, Xiaoyu ; Zhang, Yujie ; Li, Yanyan ; Wang, Di</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-e7611de7ad88f542899f1f78a10697c17a1fb2efdb2f111c5cee22e01d19c2b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Cell adhesion & migration</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell migration</topic><topic>Cell Movement - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Clonal deletion</topic><topic>Estradiol - pharmacology</topic><topic>Estrogen</topic><topic>Estrogens</topic><topic>Estrogens - pharmacology</topic><topic>Female</topic><topic>Forkhead Box Protein L2 - genetics</topic><topic>Forkhead Box Protein L2 - metabolism</topic><topic>Forkhead protein</topic><topic>FOXL2</topic><topic>GCTs</topic><topic>GPR30</topic><topic>Granulosa Cell Tumor - metabolism</topic><topic>Humans</topic><topic>Kinases</topic><topic>Middle Aged</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Point mutation</topic><topic>Protein kinase C</topic><topic>Proteins</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal transduction</topic><topic>Transcription factors</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Jun</creatorcontrib><creatorcontrib>Miao, Chunlei</creatorcontrib><creatorcontrib>Lv, Xiaoyu</creatorcontrib><creatorcontrib>Zhang, Yujie</creatorcontrib><creatorcontrib>Li, Yanyan</creatorcontrib><creatorcontrib>Wang, Di</creatorcontrib><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>Virology and AIDS Abstracts</collection><collection>Technology Research Database</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Jun</au><au>Miao, Chunlei</au><au>Lv, Xiaoyu</au><au>Zhang, Yujie</au><au>Li, Yanyan</au><au>Wang, Di</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogen regulates forkhead transcription factor 2 to promote apoptosis of human ovarian granulosa-like tumor cells</atitle><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle><addtitle>J Steroid Biochem Mol Biol</addtitle><date>2019-11</date><risdate>2019</risdate><volume>194</volume><spage>105418</spage><epage>105418</epage><pages>105418-105418</pages><artnum>105418</artnum><issn>0960-0760</issn><eissn>1879-1220</eissn><abstract>•FOXL2 is highly expressed in KGN cells and GCT tissues.•FOXL2 inhibits E2 synthesis, while E2 up-regulated the FOXL2 expression in KGN•cells.•Estrogen induces FOXL2 phosphorylation via GPCR-PKC non-genomic pathway.•Estrogen promotes cell apoptosis via FOXL2.
Granulosa cell tumors of the ovary (GCTs) are the predominant form of ovarian stromal tumors and can lead to abnormally secreted estrogen hormones. Studies have reported that forkhead transcription factor 2 (FOXL2) inhibits estrogen synthesis and its gene mutation can lead to GCTs. We unexpected found that estrogen also regulates the expression level of FOXL2. High-dose estrogen increased the expression of FOXL2 in ovarian-like granulosa (KGN) cells at both the mRNA and protein levels. However, no research has reported on the molecular regulatory mechanism and function between estrogen and FOXL2 in the development of GCTs. In this research, FOXL2 was highly expressed in KGN cells and ovarian stromal tumor tissues. Deletion of FOXL2 increased the estrogen secretion in KGN cells. In turn, high-dose estrogen increased the FOXL2 expression levels. FOXL2 was phosphorylated by GPR30 (G protein coupled receptor)-Protein kinase C (PKC) signaling pathway upon estrogen stimulation. Estrogen inhibited cell migration and proliferation, while promoting cell apoptosis. Deletion of FOXL2 inhibited the influence of estrogen on cell proliferation, migration, and apoptosis. Results suggest that estrogen via regulating FOXL2 suppresses cell proliferation and induces cell apoptosis.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31376461</pmid><doi>10.1016/j.jsbmb.2019.105418</doi><tpages>1</tpages></addata></record> |
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| subjects | Adult Aged Apoptosis Apoptosis - drug effects Cell adhesion & migration Cell growth Cell Line Cell migration Cell Movement - drug effects Cell proliferation Cell Proliferation - drug effects Clonal deletion Estradiol - pharmacology Estrogen Estrogens Estrogens - pharmacology Female Forkhead Box Protein L2 - genetics Forkhead Box Protein L2 - metabolism Forkhead protein FOXL2 GCTs GPR30 Granulosa Cell Tumor - metabolism Humans Kinases Middle Aged Ovarian cancer Ovarian Neoplasms - metabolism Point mutation Protein kinase C Proteins RNA, Messenger - metabolism Signal transduction Transcription factors Tumor cells Tumors Young Adult |
| title | Estrogen regulates forkhead transcription factor 2 to promote apoptosis of human ovarian granulosa-like tumor cells |
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