Estrogen and progestin regulate HIF-1alpha expression in ovarian cancer cell lines via the activation of Akt signaling transduction pathway
Our previous study revealed that estrogen regulates nm23-H1 expression thus promoting cell migration-invasion via activating PIK3/Akt pathway. In this study, we explored the effect of hormone on hypoxia-inducible factor-1 (HIF-1alpha), a key factor in cancer invasion and metastasis, via activation o...
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| Veröffentlicht in: | Oncology reports 2009-04, Vol.21 (4), p.893-898 |
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| creator | Hua, Keqin Din, Jingxin Cao, Qi Feng, Weiwei Zhang, Ying Yao, Liangqin Huang, Yan Zhao, Yuqin Feng, Youji |
| description | Our previous study revealed that estrogen regulates nm23-H1 expression thus promoting cell migration-invasion via activating PIK3/Akt pathway. In this study, we explored the effect of hormone on hypoxia-inducible factor-1 (HIF-1alpha), a key factor in cancer invasion and metastasis, via activation of Akt signaling transduction pathway. We treated two ovarian cancer cell lines ES-2 and SKOV3 with 17beta-estradiol, methoxyprogesterone acetate (MPA) only, or hormone combined with and Akt, MAPK pathway inhibitor, or transefected with siRNA targeting Akt sequenced with hormone. Expression of HIF-1alpha was measured by Western blotting. We observed the effect of hormone on nm23-H1 expression after the cells were transfected by siRNA targeting HIF-1alpha or treated with CoCl2 to induce HIF-1alpha overexpression. The 17beta-estradiol increased HIF-1alpha expression in ovarian cancer cells, and this upregulatory effect was abrogated by Akt inhibitor LY294002 (P |
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In this study, we explored the effect of hormone on hypoxia-inducible factor-1 (HIF-1alpha), a key factor in cancer invasion and metastasis, via activation of Akt signaling transduction pathway. We treated two ovarian cancer cell lines ES-2 and SKOV3 with 17beta-estradiol, methoxyprogesterone acetate (MPA) only, or hormone combined with and Akt, MAPK pathway inhibitor, or transefected with siRNA targeting Akt sequenced with hormone. Expression of HIF-1alpha was measured by Western blotting. We observed the effect of hormone on nm23-H1 expression after the cells were transfected by siRNA targeting HIF-1alpha or treated with CoCl2 to induce HIF-1alpha overexpression. The 17beta-estradiol increased HIF-1alpha expression in ovarian cancer cells, and this upregulatory effect was abrogated by Akt inhibitor LY294002 (P<0.05) and Akt siRNA interference (P<0.05), but not affected by MAPK inhibitor PD980059 (P>0.05). MPA had the opposite effect. Nm23-H1 protein expression in ES-2 and SKOV3 cells were decreased after treatment with 17beta-estradiol (P<0.05), whereas MPA had the opposite effect. The effect was attenuated by HIF-1alpha siRNA (P<0.05) and enhanced by HIF-1alpha overexpression after CoCl2 treatment (P<0.05). Our data suggest that estrogen and progestin regulate HIF-1alpha expression via Akt signaling pathway, affecting nm23-H1 expression in influencing cell metastasis.</description><identifier>ISSN: 1021-335X</identifier><identifier>PMID: 19287985</identifier><language>eng</language><publisher>Greece</publisher><subject>Cell Line, Tumor ; Chromones - pharmacology ; Estradiol - pharmacology ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit - analysis ; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors ; Hypoxia-Inducible Factor 1, alpha Subunit - physiology ; Medroxyprogesterone Acetate - pharmacology ; Morpholines - pharmacology ; NM23 Nucleoside Diphosphate Kinases - analysis ; Ovarian Neoplasms - pathology ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - physiology ; Signal Transduction - physiology</subject><ispartof>Oncology reports, 2009-04, Vol.21 (4), p.893-898</ispartof><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19287985$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hua, Keqin</creatorcontrib><creatorcontrib>Din, Jingxin</creatorcontrib><creatorcontrib>Cao, Qi</creatorcontrib><creatorcontrib>Feng, Weiwei</creatorcontrib><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Yao, Liangqin</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Zhao, Yuqin</creatorcontrib><creatorcontrib>Feng, Youji</creatorcontrib><title>Estrogen and progestin regulate HIF-1alpha expression in ovarian cancer cell lines via the activation of Akt signaling transduction pathway</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Our previous study revealed that estrogen regulates nm23-H1 expression thus promoting cell migration-invasion via activating PIK3/Akt pathway. In this study, we explored the effect of hormone on hypoxia-inducible factor-1 (HIF-1alpha), a key factor in cancer invasion and metastasis, via activation of Akt signaling transduction pathway. We treated two ovarian cancer cell lines ES-2 and SKOV3 with 17beta-estradiol, methoxyprogesterone acetate (MPA) only, or hormone combined with and Akt, MAPK pathway inhibitor, or transefected with siRNA targeting Akt sequenced with hormone. Expression of HIF-1alpha was measured by Western blotting. We observed the effect of hormone on nm23-H1 expression after the cells were transfected by siRNA targeting HIF-1alpha or treated with CoCl2 to induce HIF-1alpha overexpression. The 17beta-estradiol increased HIF-1alpha expression in ovarian cancer cells, and this upregulatory effect was abrogated by Akt inhibitor LY294002 (P<0.05) and Akt siRNA interference (P<0.05), but not affected by MAPK inhibitor PD980059 (P>0.05). MPA had the opposite effect. Nm23-H1 protein expression in ES-2 and SKOV3 cells were decreased after treatment with 17beta-estradiol (P<0.05), whereas MPA had the opposite effect. The effect was attenuated by HIF-1alpha siRNA (P<0.05) and enhanced by HIF-1alpha overexpression after CoCl2 treatment (P<0.05). Our data suggest that estrogen and progestin regulate HIF-1alpha expression via Akt signaling pathway, affecting nm23-H1 expression in influencing cell metastasis.</description><subject>Cell Line, Tumor</subject><subject>Chromones - pharmacology</subject><subject>Estradiol - pharmacology</subject><subject>Female</subject><subject>Humans</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - analysis</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - physiology</subject><subject>Medroxyprogesterone Acetate - pharmacology</subject><subject>Morpholines - pharmacology</subject><subject>NM23 Nucleoside Diphosphate Kinases - analysis</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - physiology</subject><subject>Signal Transduction - physiology</subject><issn>1021-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kMFOwzAQRHMA0VL4BbQnbpEcO4njY1W1FKkSlx64RRtnmxpSJ9hOod_AT5NCOc1q52m1M1fRNGE8iYXIXifRrfdvjHHJcnUTTRLFC6mKbBp9L31wXUMW0NbQn0cfjAVHzdBiIFg_r-IE236PQF-9I-9NZ2EkuiM6gxY0Wk0ONLUttMaSh6NBCHsC1MEcMZz5bgfz9wDeNBZHqIHg0Pp60L9uj2H_iae76HqHraf7i86i7Wq5XazjzcvT82K-ifsszWLSKCkReZoJiTznqs4lr1iRaeJcF7qutCpYVSlKx73eZTnnhcgV14SFlEzMose_s2Paj2GMWx6MP7-PlrrBl7lkXCUiHcGHCzhUB6rL3pkDulP53574Ae2ubU8</recordid><startdate>200904</startdate><enddate>200904</enddate><creator>Hua, Keqin</creator><creator>Din, Jingxin</creator><creator>Cao, Qi</creator><creator>Feng, Weiwei</creator><creator>Zhang, Ying</creator><creator>Yao, Liangqin</creator><creator>Huang, Yan</creator><creator>Zhao, Yuqin</creator><creator>Feng, Youji</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200904</creationdate><title>Estrogen and progestin regulate HIF-1alpha expression in ovarian cancer cell lines via the activation of Akt signaling transduction pathway</title><author>Hua, Keqin ; Din, Jingxin ; Cao, Qi ; Feng, Weiwei ; Zhang, Ying ; Yao, Liangqin ; Huang, Yan ; Zhao, Yuqin ; Feng, Youji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p545-eca7e1364537a2629d672b085ce22c8cdbc980bb9e472bcf562283692cea87703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Cell Line, Tumor</topic><topic>Chromones - pharmacology</topic><topic>Estradiol - pharmacology</topic><topic>Female</topic><topic>Humans</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - analysis</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - physiology</topic><topic>Medroxyprogesterone Acetate - pharmacology</topic><topic>Morpholines - pharmacology</topic><topic>NM23 Nucleoside Diphosphate Kinases - analysis</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>Signal Transduction - physiology</topic><toplevel>online_resources</toplevel><creatorcontrib>Hua, Keqin</creatorcontrib><creatorcontrib>Din, Jingxin</creatorcontrib><creatorcontrib>Cao, Qi</creatorcontrib><creatorcontrib>Feng, Weiwei</creatorcontrib><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Yao, Liangqin</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Zhao, Yuqin</creatorcontrib><creatorcontrib>Feng, Youji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hua, Keqin</au><au>Din, Jingxin</au><au>Cao, Qi</au><au>Feng, Weiwei</au><au>Zhang, Ying</au><au>Yao, Liangqin</au><au>Huang, Yan</au><au>Zhao, Yuqin</au><au>Feng, Youji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogen and progestin regulate HIF-1alpha expression in ovarian cancer cell lines via the activation of Akt signaling transduction pathway</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2009-04</date><risdate>2009</risdate><volume>21</volume><issue>4</issue><spage>893</spage><epage>898</epage><pages>893-898</pages><issn>1021-335X</issn><abstract>Our previous study revealed that estrogen regulates nm23-H1 expression thus promoting cell migration-invasion via activating PIK3/Akt pathway. In this study, we explored the effect of hormone on hypoxia-inducible factor-1 (HIF-1alpha), a key factor in cancer invasion and metastasis, via activation of Akt signaling transduction pathway. We treated two ovarian cancer cell lines ES-2 and SKOV3 with 17beta-estradiol, methoxyprogesterone acetate (MPA) only, or hormone combined with and Akt, MAPK pathway inhibitor, or transefected with siRNA targeting Akt sequenced with hormone. Expression of HIF-1alpha was measured by Western blotting. We observed the effect of hormone on nm23-H1 expression after the cells were transfected by siRNA targeting HIF-1alpha or treated with CoCl2 to induce HIF-1alpha overexpression. The 17beta-estradiol increased HIF-1alpha expression in ovarian cancer cells, and this upregulatory effect was abrogated by Akt inhibitor LY294002 (P<0.05) and Akt siRNA interference (P<0.05), but not affected by MAPK inhibitor PD980059 (P>0.05). MPA had the opposite effect. Nm23-H1 protein expression in ES-2 and SKOV3 cells were decreased after treatment with 17beta-estradiol (P<0.05), whereas MPA had the opposite effect. The effect was attenuated by HIF-1alpha siRNA (P<0.05) and enhanced by HIF-1alpha overexpression after CoCl2 treatment (P<0.05). Our data suggest that estrogen and progestin regulate HIF-1alpha expression via Akt signaling pathway, affecting nm23-H1 expression in influencing cell metastasis.</abstract><cop>Greece</cop><pmid>19287985</pmid><tpages>6</tpages></addata></record> |
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| subjects | Cell Line, Tumor Chromones - pharmacology Estradiol - pharmacology Female Humans Hypoxia-Inducible Factor 1, alpha Subunit - analysis Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors Hypoxia-Inducible Factor 1, alpha Subunit - physiology Medroxyprogesterone Acetate - pharmacology Morpholines - pharmacology NM23 Nucleoside Diphosphate Kinases - analysis Ovarian Neoplasms - pathology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - physiology Signal Transduction - physiology |
| title | Estrogen and progestin regulate HIF-1alpha expression in ovarian cancer cell lines via the activation of Akt signaling transduction pathway |
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