Role of phosphatidylinositol signaling pathway in the development of cross-resistance of tumor cells to hormonal cytostatics and hypoxia
Long-term in vitro culturing of CaOv ovarian adenocarcinoma cells in the presence of a synthetic analogue of glucocorticoid hormone dexamethasone allowed us to obtain a subline of CaOv/D cells resistant to the antiproliferative effect of dexamethasone and characterized by high resistance to hypoxia....
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Veröffentlicht in: | Bulletin of experimental biology and medicine 2007-02, Vol.143 (2), p.244-247 |
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creator | Shatskaya, V A Pavlichenko, O V Krasil'nikov, M A |
description | Long-term in vitro culturing of CaOv ovarian adenocarcinoma cells in the presence of a synthetic analogue of glucocorticoid hormone dexamethasone allowed us to obtain a subline of CaOv/D cells resistant to the antiproliferative effect of dexamethasone and characterized by high resistance to hypoxia. It was found that CaOv/D cells are characterized by constitutive increase in phosphatidylinositol 3-kinase expression and hypersecretion of vascular endothelial growth factor VEGF-A. Culturing of cells under hypoxic conditions was accompanied by a significant increase in phosphatidylinositol 3-kinase expression and VEGF-A synthesis. Experiments with cell transfection with phosphatidylinositol 3-kinase catalytic subunit proved its participation in the regulation of VEGF-A synthesis and maintenance of cell growth under condition of hypoxia. Our results indicate that coordinated activation of phosphatidylinositol 3-kinase and VEGF-A can be a factor determining the development of cross-resistance of tumor cells to hormonal cytostatics and hypoxia. |
doi_str_mv | 10.1007/s10517-007-0061-7 |
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It was found that CaOv/D cells are characterized by constitutive increase in phosphatidylinositol 3-kinase expression and hypersecretion of vascular endothelial growth factor VEGF-A. Culturing of cells under hypoxic conditions was accompanied by a significant increase in phosphatidylinositol 3-kinase expression and VEGF-A synthesis. Experiments with cell transfection with phosphatidylinositol 3-kinase catalytic subunit proved its participation in the regulation of VEGF-A synthesis and maintenance of cell growth under condition of hypoxia. 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Our results indicate that coordinated activation of phosphatidylinositol 3-kinase and VEGF-A can be a factor determining the development of cross-resistance of tumor cells to hormonal cytostatics and hypoxia.</description><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Antineoplastic Agents, Hormonal - pharmacology</subject><subject>Cell Hypoxia</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Dexamethasone - pharmacology</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphatidylinositols - metabolism</subject><subject>Phosphatidylinositols - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Signal Transduction - physiology</subject><subject>Time Factors</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>0007-4888</issn><issn>1573-8221</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><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>eNpdkc1u3SAQhVHVqrn5eYBuKtRFd04ZsAEvoyhtI0WqVLVrxAUcE9nGAdzEb9DHLs69UqUsEDPiO0fDHIQ-ALkEQsSXBKQBUZWyHA6VeIN20AhWSUrhLdqR7aWWUp6g05QetrZg79EJiFYQCnSH_v4Mg8Ohw3Mf0tzr7O06-Ckkn8OAk7-fdGnv8axz_6RX7Cece4et--OGMI9uypvYxJBSFV3yKevJvBjmZQwRGzcMCeeA-xDHUMywWXMoVPYmYT1Z3K9zePb6HL3r9JDcxfE-Q7-_3vy6_l7d_fh2e311VxkqZK4Y47SrWyEb27ZdA3sG1gAQa2lNOec1EW3TUs64rDXsjdTckNYaxjota7NnZ-jzwXeO4XFxKavRp21KPbmwJFV0DWlaXsBPr8CHsMTyg6QosKYsk9ECwQF62UB0nZqjH3VcFRC1ZaQOGamt3DJSomg-Ho2X_ejsf8UxFPYPL_uOpw</recordid><startdate>200702</startdate><enddate>200702</enddate><creator>Shatskaya, V A</creator><creator>Pavlichenko, O V</creator><creator>Krasil'nikov, M A</creator><general>Springer Nature B.V</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</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>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200702</creationdate><title>Role of phosphatidylinositol signaling pathway in the development of cross-resistance of tumor cells to hormonal cytostatics and hypoxia</title><author>Shatskaya, V A ; 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subjects | Adenocarcinoma - metabolism Adenocarcinoma - pathology Antineoplastic Agents, Hormonal - pharmacology Cell Hypoxia Cell Line, Tumor Cell Proliferation - drug effects Dexamethasone - pharmacology Drug Resistance, Neoplasm Female Humans Immunoblotting Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Phosphatidylinositols - metabolism Phosphatidylinositols - physiology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction - physiology Time Factors Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism |
title | Role of phosphatidylinositol signaling pathway in the development of cross-resistance of tumor cells to hormonal cytostatics and hypoxia |
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