Aberrant Regulation of Transforming Growth Factor-α during the Establishment of Growth Arrest and Quiescence of Growth Factor Independent Cells
Autocrine transforming growth factor α (TGFα) is an important positive growth effector in malignant cells and plays a significant role in generating the growth factor-independent phenotype associated with malignant progression. However, the molecular mechanisms by which TGFα confers a growth adva...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 1998-04, Vol.273 (15), p.9214 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 15 |
| container_start_page | 9214 |
| container_title | The Journal of biological chemistry |
| container_volume | 273 |
| creator | Gillian M. Howell Lisa E. Humphrey Rana A. Awwad Degeng Wang Alan Koterba Basker Periyasamy Junhua Yang Wenhui Li James K. V. Willson Barry L. Ziober Kevin Coleman Joan Carboni Mark Lynch Michael G. Brattain |
| description | Autocrine transforming growth factor α (TGFα) is an important positive growth effector in malignant cells and plays a significant
role in generating the growth factor-independent phenotype associated with malignant progression. However, the molecular mechanisms
by which TGFα confers a growth advantage in progression is poorly understood. The highly tumorigenic cell line HCT116 up-regulates
TGFα mRNA expression during growth arrest, whereas the poorly tumorigenic growth factor-dependent FET cell line down-regulates
TGFα mRNA expression as it becomes quiescent. We have identified a 25-bp sequence at â201 to â225 within the TGFα promoter
which mediates the differential regulation of TGFα expression during quiescence establishment in these two cell lines. This
same sequence confers TGFα promoter responsiveness to exogenous growth factor or autocrine TGFα. The abberant upregulation
of TGFα mRNA in quiescent HCT116 cells may allow them to return to the dividing state under more stringent conditions (nutrient
replenishment alone) then quiescent FET cells (requires nutrients and growth factors). Antisense TGFα approaches showed that
the dysregulated TGFα expression in quiescent HCT116 cells is a function of the strong TGFα autocrine loop (not inhibited
by blocking antibodies) in these cells. |
| doi_str_mv | 10.1074/jbc.273.15.9214 |
| format | Article |
| fullrecord | <record><control><sourceid>highwire</sourceid><recordid>TN_cdi_highwire_biochem_273_15_9214</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>273_15_9214</sourcerecordid><originalsourceid>FETCH-highwire_biochem_273_15_92143</originalsourceid><addsrcrecordid>eNqNT7tOwzAUtRCohMfMaok5wY5jtRmrqqWMoA5skePcxK4cG9mO-hcM_Am_AD-GKzowcoZ7pHse0kHojpKCknn1sG9lUc5ZQXlRl7Q6QxklC5YzTl_PUUZISfO65ItLdBXCniRUNZ2hWc0ZrynL0MeyBe-FjfgFhsmIqJ3Frse79Au986O2A3707hAV3ggZnc-_378-cTf5oxIV4HWIojU6qBFSTcqe7EvvIUQsbIefJw1BgpXwR_-tw0-2gzdIJ4VXYEy4QRe9MAFuT3yN7jfr3WqbKz2og_bQtNpJBWOThjeUN8fh7H-uH6c7YD0</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Aberrant Regulation of Transforming Growth Factor-α during the Establishment of Growth Arrest and Quiescence of Growth Factor Independent Cells</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Gillian M. Howell ; Lisa E. Humphrey ; Rana A. Awwad ; Degeng Wang ; Alan Koterba ; Basker Periyasamy ; Junhua Yang ; Wenhui Li ; James K. V. Willson ; Barry L. Ziober ; Kevin Coleman ; Joan Carboni ; Mark Lynch ; Michael G. Brattain</creator><creatorcontrib>Gillian M. Howell ; Lisa E. Humphrey ; Rana A. Awwad ; Degeng Wang ; Alan Koterba ; Basker Periyasamy ; Junhua Yang ; Wenhui Li ; James K. V. Willson ; Barry L. Ziober ; Kevin Coleman ; Joan Carboni ; Mark Lynch ; Michael G. Brattain</creatorcontrib><description>Autocrine transforming growth factor α (TGFα) is an important positive growth effector in malignant cells and plays a significant
role in generating the growth factor-independent phenotype associated with malignant progression. However, the molecular mechanisms
by which TGFα confers a growth advantage in progression is poorly understood. The highly tumorigenic cell line HCT116 up-regulates
TGFα mRNA expression during growth arrest, whereas the poorly tumorigenic growth factor-dependent FET cell line down-regulates
TGFα mRNA expression as it becomes quiescent. We have identified a 25-bp sequence at â201 to â225 within the TGFα promoter
which mediates the differential regulation of TGFα expression during quiescence establishment in these two cell lines. This
same sequence confers TGFα promoter responsiveness to exogenous growth factor or autocrine TGFα. The abberant upregulation
of TGFα mRNA in quiescent HCT116 cells may allow them to return to the dividing state under more stringent conditions (nutrient
replenishment alone) then quiescent FET cells (requires nutrients and growth factors). Antisense TGFα approaches showed that
the dysregulated TGFα expression in quiescent HCT116 cells is a function of the strong TGFα autocrine loop (not inhibited
by blocking antibodies) in these cells.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.273.15.9214</identifier><identifier>PMID: 9535913</identifier><language>eng</language><publisher>American Society for Biochemistry and Molecular Biology</publisher><ispartof>The Journal of biological chemistry, 1998-04, Vol.273 (15), p.9214</ispartof><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>314,776,780,27903,27904</link.rule.ids></links><search><creatorcontrib>Gillian M. Howell</creatorcontrib><creatorcontrib>Lisa E. Humphrey</creatorcontrib><creatorcontrib>Rana A. Awwad</creatorcontrib><creatorcontrib>Degeng Wang</creatorcontrib><creatorcontrib>Alan Koterba</creatorcontrib><creatorcontrib>Basker Periyasamy</creatorcontrib><creatorcontrib>Junhua Yang</creatorcontrib><creatorcontrib>Wenhui Li</creatorcontrib><creatorcontrib>James K. V. Willson</creatorcontrib><creatorcontrib>Barry L. Ziober</creatorcontrib><creatorcontrib>Kevin Coleman</creatorcontrib><creatorcontrib>Joan Carboni</creatorcontrib><creatorcontrib>Mark Lynch</creatorcontrib><creatorcontrib>Michael G. Brattain</creatorcontrib><title>Aberrant Regulation of Transforming Growth Factor-α during the Establishment of Growth Arrest and Quiescence of Growth Factor Independent Cells</title><title>The Journal of biological chemistry</title><description>Autocrine transforming growth factor α (TGFα) is an important positive growth effector in malignant cells and plays a significant
role in generating the growth factor-independent phenotype associated with malignant progression. However, the molecular mechanisms
by which TGFα confers a growth advantage in progression is poorly understood. The highly tumorigenic cell line HCT116 up-regulates
TGFα mRNA expression during growth arrest, whereas the poorly tumorigenic growth factor-dependent FET cell line down-regulates
TGFα mRNA expression as it becomes quiescent. We have identified a 25-bp sequence at â201 to â225 within the TGFα promoter
which mediates the differential regulation of TGFα expression during quiescence establishment in these two cell lines. This
same sequence confers TGFα promoter responsiveness to exogenous growth factor or autocrine TGFα. The abberant upregulation
of TGFα mRNA in quiescent HCT116 cells may allow them to return to the dividing state under more stringent conditions (nutrient
replenishment alone) then quiescent FET cells (requires nutrients and growth factors). Antisense TGFα approaches showed that
the dysregulated TGFα expression in quiescent HCT116 cells is a function of the strong TGFα autocrine loop (not inhibited
by blocking antibodies) in these cells.</description><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqNT7tOwzAUtRCohMfMaok5wY5jtRmrqqWMoA5skePcxK4cG9mO-hcM_Am_AD-GKzowcoZ7pHse0kHojpKCknn1sG9lUc5ZQXlRl7Q6QxklC5YzTl_PUUZISfO65ItLdBXCniRUNZ2hWc0ZrynL0MeyBe-FjfgFhsmIqJ3Frse79Au986O2A3707hAV3ggZnc-_378-cTf5oxIV4HWIojU6qBFSTcqe7EvvIUQsbIefJw1BgpXwR_-tw0-2gzdIJ4VXYEy4QRe9MAFuT3yN7jfr3WqbKz2og_bQtNpJBWOThjeUN8fh7H-uH6c7YD0</recordid><startdate>19980410</startdate><enddate>19980410</enddate><creator>Gillian M. Howell</creator><creator>Lisa E. Humphrey</creator><creator>Rana A. Awwad</creator><creator>Degeng Wang</creator><creator>Alan Koterba</creator><creator>Basker Periyasamy</creator><creator>Junhua Yang</creator><creator>Wenhui Li</creator><creator>James K. V. Willson</creator><creator>Barry L. Ziober</creator><creator>Kevin Coleman</creator><creator>Joan Carboni</creator><creator>Mark Lynch</creator><creator>Michael G. Brattain</creator><general>American Society for Biochemistry and Molecular Biology</general><scope/></search><sort><creationdate>19980410</creationdate><title>Aberrant Regulation of Transforming Growth Factor-α during the Establishment of Growth Arrest and Quiescence of Growth Factor Independent Cells</title><author>Gillian M. Howell ; Lisa E. Humphrey ; Rana A. Awwad ; Degeng Wang ; Alan Koterba ; Basker Periyasamy ; Junhua Yang ; Wenhui Li ; James K. V. Willson ; Barry L. Ziober ; Kevin Coleman ; Joan Carboni ; Mark Lynch ; Michael G. Brattain</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-highwire_biochem_273_15_92143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gillian M. Howell</creatorcontrib><creatorcontrib>Lisa E. Humphrey</creatorcontrib><creatorcontrib>Rana A. Awwad</creatorcontrib><creatorcontrib>Degeng Wang</creatorcontrib><creatorcontrib>Alan Koterba</creatorcontrib><creatorcontrib>Basker Periyasamy</creatorcontrib><creatorcontrib>Junhua Yang</creatorcontrib><creatorcontrib>Wenhui Li</creatorcontrib><creatorcontrib>James K. V. Willson</creatorcontrib><creatorcontrib>Barry L. Ziober</creatorcontrib><creatorcontrib>Kevin Coleman</creatorcontrib><creatorcontrib>Joan Carboni</creatorcontrib><creatorcontrib>Mark Lynch</creatorcontrib><creatorcontrib>Michael G. Brattain</creatorcontrib><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gillian M. Howell</au><au>Lisa E. Humphrey</au><au>Rana A. Awwad</au><au>Degeng Wang</au><au>Alan Koterba</au><au>Basker Periyasamy</au><au>Junhua Yang</au><au>Wenhui Li</au><au>James K. V. Willson</au><au>Barry L. Ziober</au><au>Kevin Coleman</au><au>Joan Carboni</au><au>Mark Lynch</au><au>Michael G. Brattain</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant Regulation of Transforming Growth Factor-α during the Establishment of Growth Arrest and Quiescence of Growth Factor Independent Cells</atitle><jtitle>The Journal of biological chemistry</jtitle><date>1998-04-10</date><risdate>1998</risdate><volume>273</volume><issue>15</issue><spage>9214</spage><pages>9214-</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Autocrine transforming growth factor α (TGFα) is an important positive growth effector in malignant cells and plays a significant
role in generating the growth factor-independent phenotype associated with malignant progression. However, the molecular mechanisms
by which TGFα confers a growth advantage in progression is poorly understood. The highly tumorigenic cell line HCT116 up-regulates
TGFα mRNA expression during growth arrest, whereas the poorly tumorigenic growth factor-dependent FET cell line down-regulates
TGFα mRNA expression as it becomes quiescent. We have identified a 25-bp sequence at â201 to â225 within the TGFα promoter
which mediates the differential regulation of TGFα expression during quiescence establishment in these two cell lines. This
same sequence confers TGFα promoter responsiveness to exogenous growth factor or autocrine TGFα. The abberant upregulation
of TGFα mRNA in quiescent HCT116 cells may allow them to return to the dividing state under more stringent conditions (nutrient
replenishment alone) then quiescent FET cells (requires nutrients and growth factors). Antisense TGFα approaches showed that
the dysregulated TGFα expression in quiescent HCT116 cells is a function of the strong TGFα autocrine loop (not inhibited
by blocking antibodies) in these cells.</abstract><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>9535913</pmid><doi>10.1074/jbc.273.15.9214</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1998-04, Vol.273 (15), p.9214 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_highwire_biochem_273_15_9214 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| title | Aberrant Regulation of Transforming Growth Factor-α during the Establishment of Growth Arrest and Quiescence of Growth Factor Independent Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T10%3A54%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-highwire&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Aberrant%20Regulation%20of%20Transforming%20Growth%20Factor-%C3%8E%C2%B1%20during%20the%20Establishment%20of%20Growth%20Arrest%20and%20Quiescence%20of%20Growth%20Factor%20Independent%20Cells&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Gillian%20M.%20Howell&rft.date=1998-04-10&rft.volume=273&rft.issue=15&rft.spage=9214&rft.pages=9214-&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.273.15.9214&rft_dat=%3Chighwire%3E273_15_9214%3C/highwire%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/9535913&rfr_iscdi=true |