Tamoxifen Modulates Apoptotic Pathways in Primary Endometrial Cell Cultures
Clinical data indicate that tamoxifen (TAM) therapy may cause an increased risk of endometrial pathology in postmenopausal but not in premenopausal women. Molecular mechanisms of the uterotrophic activity of TAM have not been clearly established nor its relevance to apoptosis in endometrial cells. T...
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| Veröffentlicht in: | Clinical cancer research 2001-02, Vol.7 (2), p.415-420 |
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| creator | STACKIEVICZ, Rodica DRUCKER, Liat RADNAY, Judith BEYTH, Yoram YARKONI, Shai COHEN, Ilan |
| description | Clinical data indicate that tamoxifen (TAM) therapy may cause an
increased risk of endometrial pathology in postmenopausal but not in
premenopausal women. Molecular mechanisms of the uterotrophic activity
of TAM have not been clearly established nor its relevance to apoptosis
in endometrial cells. The present study was implemented to evaluate the
apoptotic effect of TAM on primary endometrial cell cultures in the
presence or absence of steroid hormones (SHs). A total of 14 primary
endometrial cell cultures were established and maintained both with and
without SHs. Cell cultures were treated for 24 h with either 20μ
m TAM or 10 n m estradiol. Apoptotic cells
presented in a pre-G 1 peak and the expression of bcl-2 were
studied using flow cytometry. All endometrial cell cultures maintained
in a SH-containing environment, except one, responded to TAM by a
significant increase ( P = 0.03) in the
pre-G 1 cell fraction, indicating a proapoptotic effect. A
significant ( P = 0.03) reduction in the
pre-G 1 peak equivalent to an antiapoptotic response was
observed in 6 of 13 cell cultures maintained in a SH-deficient
environment. In 4 of 10 cell cultures evaluated in both media, the
pre-G 1 population was medium dependent. In 8 of 10 cultures
evaluated for Bcl2 levels, no trend was found in either media, but a
dependency on SH content was observed. Comparison between effects of
TAM and estradiol demonstrated identical trends, regardless of the
menstrual phase or SH content in cell environments. These results
suggest that TAM acts as an estrogen agonist on endometrial tissue in
both environments. We conclude that TAM modulates apoptotic pathways in
primary endometrial cell cultures. The SH content in the cell
environment influences the apoptotic effect of TAM and determines the
propensity for a cell to undergo apoptosis or, on the contrary, to
resist apoptotic death in response to TAM treatment. This is in
concordance with the observed clinical risk of endometrial pathologies
in postmenopausal versus premenopausal women. |
| format | Article |
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increased risk of endometrial pathology in postmenopausal but not in
premenopausal women. Molecular mechanisms of the uterotrophic activity
of TAM have not been clearly established nor its relevance to apoptosis
in endometrial cells. The present study was implemented to evaluate the
apoptotic effect of TAM on primary endometrial cell cultures in the
presence or absence of steroid hormones (SHs). A total of 14 primary
endometrial cell cultures were established and maintained both with and
without SHs. Cell cultures were treated for 24 h with either 20μ
m TAM or 10 n m estradiol. Apoptotic cells
presented in a pre-G 1 peak and the expression of bcl-2 were
studied using flow cytometry. All endometrial cell cultures maintained
in a SH-containing environment, except one, responded to TAM by a
significant increase ( P = 0.03) in the
pre-G 1 cell fraction, indicating a proapoptotic effect. A
significant ( P = 0.03) reduction in the
pre-G 1 peak equivalent to an antiapoptotic response was
observed in 6 of 13 cell cultures maintained in a SH-deficient
environment. In 4 of 10 cell cultures evaluated in both media, the
pre-G 1 population was medium dependent. In 8 of 10 cultures
evaluated for Bcl2 levels, no trend was found in either media, but a
dependency on SH content was observed. Comparison between effects of
TAM and estradiol demonstrated identical trends, regardless of the
menstrual phase or SH content in cell environments. These results
suggest that TAM acts as an estrogen agonist on endometrial tissue in
both environments. We conclude that TAM modulates apoptotic pathways in
primary endometrial cell cultures. The SH content in the cell
environment influences the apoptotic effect of TAM and determines the
propensity for a cell to undergo apoptosis or, on the contrary, to
resist apoptotic death in response to TAM treatment. This is in
concordance with the observed clinical risk of endometrial pathologies
in postmenopausal versus premenopausal women.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 11234898</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Antineoplastic Agents, Hormonal - pharmacology ; Apoptosis - drug effects ; Biological and medical sciences ; Cell Line ; Drug toxicity and drugs side effects treatment ; Endometrial Neoplasms - drug therapy ; Endometrial Neoplasms - metabolism ; Endometrium - cytology ; Endometrium - drug effects ; Endometrium - metabolism ; Estradiol - pharmacology ; Female ; Humans ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Receptors, Estrogen - metabolism ; Signal Transduction ; Tamoxifen - pharmacology ; Toxicity: urogenital system ; Tumor Cells, Cultured</subject><ispartof>Clinical cancer research, 2001-02, Vol.7 (2), p.415-420</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=902709$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11234898$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>STACKIEVICZ, Rodica</creatorcontrib><creatorcontrib>DRUCKER, Liat</creatorcontrib><creatorcontrib>RADNAY, Judith</creatorcontrib><creatorcontrib>BEYTH, Yoram</creatorcontrib><creatorcontrib>YARKONI, Shai</creatorcontrib><creatorcontrib>COHEN, Ilan</creatorcontrib><title>Tamoxifen Modulates Apoptotic Pathways in Primary Endometrial Cell Cultures</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Clinical data indicate that tamoxifen (TAM) therapy may cause an
increased risk of endometrial pathology in postmenopausal but not in
premenopausal women. Molecular mechanisms of the uterotrophic activity
of TAM have not been clearly established nor its relevance to apoptosis
in endometrial cells. The present study was implemented to evaluate the
apoptotic effect of TAM on primary endometrial cell cultures in the
presence or absence of steroid hormones (SHs). A total of 14 primary
endometrial cell cultures were established and maintained both with and
without SHs. Cell cultures were treated for 24 h with either 20μ
m TAM or 10 n m estradiol. Apoptotic cells
presented in a pre-G 1 peak and the expression of bcl-2 were
studied using flow cytometry. All endometrial cell cultures maintained
in a SH-containing environment, except one, responded to TAM by a
significant increase ( P = 0.03) in the
pre-G 1 cell fraction, indicating a proapoptotic effect. A
significant ( P = 0.03) reduction in the
pre-G 1 peak equivalent to an antiapoptotic response was
observed in 6 of 13 cell cultures maintained in a SH-deficient
environment. In 4 of 10 cell cultures evaluated in both media, the
pre-G 1 population was medium dependent. In 8 of 10 cultures
evaluated for Bcl2 levels, no trend was found in either media, but a
dependency on SH content was observed. Comparison between effects of
TAM and estradiol demonstrated identical trends, regardless of the
menstrual phase or SH content in cell environments. These results
suggest that TAM acts as an estrogen agonist on endometrial tissue in
both environments. We conclude that TAM modulates apoptotic pathways in
primary endometrial cell cultures. The SH content in the cell
environment influences the apoptotic effect of TAM and determines the
propensity for a cell to undergo apoptosis or, on the contrary, to
resist apoptotic death in response to TAM treatment. This is in
concordance with the observed clinical risk of endometrial pathologies
in postmenopausal versus premenopausal women.</description><subject>Adult</subject><subject>Antineoplastic Agents, Hormonal - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Endometrial Neoplasms - drug therapy</subject><subject>Endometrial Neoplasms - metabolism</subject><subject>Endometrium - cytology</subject><subject>Endometrium - drug effects</subject><subject>Endometrium - metabolism</subject><subject>Estradiol - pharmacology</subject><subject>Female</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Signal Transduction</subject><subject>Tamoxifen - pharmacology</subject><subject>Toxicity: urogenital system</subject><subject>Tumor Cells, Cultured</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNj01LAzEQhhdRbK3-BVkQvC0kk-wmeyylfmDFHuo5TLNZN7IfNclS---NWMXLzBwe3nmfk2RK81xkDIr8NN5EyIxwBpPkwvt3QiinhJ8nE0qBcVnKafK0wW74tLXp0-ehGlsMxqfz3bALQ7A6XWNo9njwqe3TtbMdukO67KuhM8FZbNOFaeMY2zA64y-Tsxpbb66Oe5a83i03i4ds9XL_uJivsgaKImQSuDSMCAEA2wJkWXNJqZB5LbUsOVJDTF6bEpmGCkEXEOtKyRighJKVbJbc_uTu3PAxGh9UZ72OTbA3w-iVIMV3tozg9REct52p1O7HQP3qR-DmCKDX2NYOe239H1cSEOTfv8a-NXvrjNKRMy4qG3S6UUKB4jRnXyOecB4</recordid><startdate>20010201</startdate><enddate>20010201</enddate><creator>STACKIEVICZ, Rodica</creator><creator>DRUCKER, Liat</creator><creator>RADNAY, Judith</creator><creator>BEYTH, Yoram</creator><creator>YARKONI, Shai</creator><creator>COHEN, Ilan</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010201</creationdate><title>Tamoxifen Modulates Apoptotic Pathways in Primary Endometrial Cell Cultures</title><author>STACKIEVICZ, Rodica ; DRUCKER, Liat ; RADNAY, Judith ; BEYTH, Yoram ; YARKONI, Shai ; COHEN, Ilan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h266t-8248e3077222b6289f4811785f8c894a1e0e5fe9a3c2da2c6211288332a829393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Antineoplastic Agents, Hormonal - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Endometrial Neoplasms - drug therapy</topic><topic>Endometrial Neoplasms - metabolism</topic><topic>Endometrium - cytology</topic><topic>Endometrium - drug effects</topic><topic>Endometrium - metabolism</topic><topic>Estradiol - pharmacology</topic><topic>Female</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Signal Transduction</topic><topic>Tamoxifen - pharmacology</topic><topic>Toxicity: urogenital system</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STACKIEVICZ, Rodica</creatorcontrib><creatorcontrib>DRUCKER, Liat</creatorcontrib><creatorcontrib>RADNAY, Judith</creatorcontrib><creatorcontrib>BEYTH, Yoram</creatorcontrib><creatorcontrib>YARKONI, Shai</creatorcontrib><creatorcontrib>COHEN, Ilan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STACKIEVICZ, Rodica</au><au>DRUCKER, Liat</au><au>RADNAY, Judith</au><au>BEYTH, Yoram</au><au>YARKONI, Shai</au><au>COHEN, Ilan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tamoxifen Modulates Apoptotic Pathways in Primary Endometrial Cell Cultures</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2001-02-01</date><risdate>2001</risdate><volume>7</volume><issue>2</issue><spage>415</spage><epage>420</epage><pages>415-420</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Clinical data indicate that tamoxifen (TAM) therapy may cause an
increased risk of endometrial pathology in postmenopausal but not in
premenopausal women. Molecular mechanisms of the uterotrophic activity
of TAM have not been clearly established nor its relevance to apoptosis
in endometrial cells. The present study was implemented to evaluate the
apoptotic effect of TAM on primary endometrial cell cultures in the
presence or absence of steroid hormones (SHs). A total of 14 primary
endometrial cell cultures were established and maintained both with and
without SHs. Cell cultures were treated for 24 h with either 20μ
m TAM or 10 n m estradiol. Apoptotic cells
presented in a pre-G 1 peak and the expression of bcl-2 were
studied using flow cytometry. All endometrial cell cultures maintained
in a SH-containing environment, except one, responded to TAM by a
significant increase ( P = 0.03) in the
pre-G 1 cell fraction, indicating a proapoptotic effect. A
significant ( P = 0.03) reduction in the
pre-G 1 peak equivalent to an antiapoptotic response was
observed in 6 of 13 cell cultures maintained in a SH-deficient
environment. In 4 of 10 cell cultures evaluated in both media, the
pre-G 1 population was medium dependent. In 8 of 10 cultures
evaluated for Bcl2 levels, no trend was found in either media, but a
dependency on SH content was observed. Comparison between effects of
TAM and estradiol demonstrated identical trends, regardless of the
menstrual phase or SH content in cell environments. These results
suggest that TAM acts as an estrogen agonist on endometrial tissue in
both environments. We conclude that TAM modulates apoptotic pathways in
primary endometrial cell cultures. The SH content in the cell
environment influences the apoptotic effect of TAM and determines the
propensity for a cell to undergo apoptosis or, on the contrary, to
resist apoptotic death in response to TAM treatment. This is in
concordance with the observed clinical risk of endometrial pathologies
in postmenopausal versus premenopausal women.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11234898</pmid><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2001-02, Vol.7 (2), p.415-420 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70672228 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Antineoplastic Agents, Hormonal - pharmacology Apoptosis - drug effects Biological and medical sciences Cell Line Drug toxicity and drugs side effects treatment Endometrial Neoplasms - drug therapy Endometrial Neoplasms - metabolism Endometrium - cytology Endometrium - drug effects Endometrium - metabolism Estradiol - pharmacology Female Humans Medical sciences Middle Aged Pharmacology. Drug treatments Proto-Oncogene Proteins c-bcl-2 - metabolism Receptors, Estrogen - metabolism Signal Transduction Tamoxifen - pharmacology Toxicity: urogenital system Tumor Cells, Cultured |
| title | Tamoxifen Modulates Apoptotic Pathways in Primary Endometrial Cell Cultures |
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