Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation
The 40S ribosomal S6 kinase 1 (S6K1) is an important regulator of cell growth. Expression of S6K1 is often elevated in breast cancer cells. However, the transcriptional mechanism of S6K1 overexpression is not understood. In this report, we demonstrate that estrogen activates expression of S6K1 via e...
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| Veröffentlicht in: | Oncogene 2012-12, Vol.31 (49), p.5073-5080 |
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| creator | Maruani, D M Spiegel, T N Harris, E N Shachter, A S Unger, H A Herrero-González, S Holz, M K |
| description | The 40S ribosomal S6 kinase 1 (S6K1) is an important regulator of cell growth. Expression of S6K1 is often elevated in breast cancer cells. However, the transcriptional mechanism of S6K1 overexpression is not understood. In this report, we demonstrate that estrogen activates expression of S6K1 via estrogen receptor (ER)α in ER-positive breast cancer cells. We also show that estrogen acts on the proximal promoter of the S6K1 gene in a mechanism involving the transcriptional factor GATA-3. Finally, we provide data that support the importance of estrogenic regulation of S6K1 expression in breast cancer cell proliferation. S6K1 directly phosphorylates and regulates ligand-independent activity of ERα, while ERα upregulates S6K1 expression. This S6K1–ERα relationship creates a positive feed-forward loop in control of breast cancer cell proliferation. Furthermore, the co-dependent association between S6K1 and ERα may be exploited in the development of targeted breast cancer therapies. |
| doi_str_mv | 10.1038/onc.2011.657 |
| format | Article |
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Expression of S6K1 is often elevated in breast cancer cells. However, the transcriptional mechanism of S6K1 overexpression is not understood. In this report, we demonstrate that estrogen activates expression of S6K1 via estrogen receptor (ER)α in ER-positive breast cancer cells. We also show that estrogen acts on the proximal promoter of the S6K1 gene in a mechanism involving the transcriptional factor GATA-3. Finally, we provide data that support the importance of estrogenic regulation of S6K1 expression in breast cancer cell proliferation. S6K1 directly phosphorylates and regulates ligand-independent activity of ERα, while ERα upregulates S6K1 expression. This S6K1–ERα relationship creates a positive feed-forward loop in control of breast cancer cell proliferation. Furthermore, the co-dependent association between S6K1 and ERα may be exploited in the development of targeted breast cancer therapies.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2011.657</identifier><identifier>PMID: 22286763</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136/2091 ; 631/67/1347 ; 631/80/86 ; Animals ; Apoptosis ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer cells ; Cancer therapies ; Cell Biology ; Cell growth ; Cell Proliferation ; Cellular biology ; Data processing ; Development and progression ; Estradiol - pharmacology ; Estrogen ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Estrogen receptors ; Estrogens ; Feedback, Physiological ; Female ; GATA-3 protein ; GATA3 Transcription Factor - genetics ; GATA3 Transcription Factor - metabolism ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Genetic regulation ; Growth ; Health aspects ; Human Genetics ; Humans ; Internal Medicine ; Kinases ; Mammary Glands, Animal - drug effects ; Mammary Glands, Animal - metabolism ; MCF-7 Cells ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred Strains ; Oncology ; original-article ; Phosphorylation ; Promoter Regions, Genetic ; Promoters ; Ribosomal protein S6 kinase ; Ribosomal Protein S6 Kinases, 70-kDa - genetics ; Ribosomal Protein S6 Kinases, 70-kDa - metabolism ; Tamoxifen - analogs & derivatives ; Tamoxifen - pharmacology ; Transcription ; Xenoestrogens</subject><ispartof>Oncogene, 2012-12, Vol.31 (49), p.5073-5080</ispartof><rights>Macmillan Publishers Limited 2012</rights><rights>COPYRIGHT 2012 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 6, 2012</rights><rights>Macmillan Publishers Limited 2012.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c644t-4e0986eb1128c44bb6d4b3fa750c8f168d6b00d463ebbd3dfcfc1eebd5dd2f3b3</citedby><cites>FETCH-LOGICAL-c644t-4e0986eb1128c44bb6d4b3fa750c8f168d6b00d463ebbd3dfcfc1eebd5dd2f3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2011.657$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2011.657$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22286763$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maruani, D M</creatorcontrib><creatorcontrib>Spiegel, T N</creatorcontrib><creatorcontrib>Harris, E N</creatorcontrib><creatorcontrib>Shachter, A S</creatorcontrib><creatorcontrib>Unger, H A</creatorcontrib><creatorcontrib>Herrero-González, S</creatorcontrib><creatorcontrib>Holz, M K</creatorcontrib><title>Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>The 40S ribosomal S6 kinase 1 (S6K1) is an important regulator of cell growth. Expression of S6K1 is often elevated in breast cancer cells. However, the transcriptional mechanism of S6K1 overexpression is not understood. In this report, we demonstrate that estrogen activates expression of S6K1 via estrogen receptor (ER)α in ER-positive breast cancer cells. We also show that estrogen acts on the proximal promoter of the S6K1 gene in a mechanism involving the transcriptional factor GATA-3. Finally, we provide data that support the importance of estrogenic regulation of S6K1 expression in breast cancer cell proliferation. S6K1 directly phosphorylates and regulates ligand-independent activity of ERα, while ERα upregulates S6K1 expression. This S6K1–ERα relationship creates a positive feed-forward loop in control of breast cancer cell proliferation. Furthermore, the co-dependent association between S6K1 and ERα may be exploited in the development of targeted breast cancer therapies.</description><subject>631/136/2091</subject><subject>631/67/1347</subject><subject>631/80/86</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Cell Biology</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Cellular biology</subject><subject>Data processing</subject><subject>Development and progression</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Feedback, Physiological</subject><subject>Female</subject><subject>GATA-3 protein</subject><subject>GATA3 Transcription Factor - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maruani, D M</au><au>Spiegel, T N</au><au>Harris, E N</au><au>Shachter, A S</au><au>Unger, H A</au><au>Herrero-González, S</au><au>Holz, M K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2012-12-06</date><risdate>2012</risdate><volume>31</volume><issue>49</issue><spage>5073</spage><epage>5080</epage><pages>5073-5080</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>The 40S ribosomal S6 kinase 1 (S6K1) is an important regulator of cell growth. Expression of S6K1 is often elevated in breast cancer cells. However, the transcriptional mechanism of S6K1 overexpression is not understood. In this report, we demonstrate that estrogen activates expression of S6K1 via estrogen receptor (ER)α in ER-positive breast cancer cells. We also show that estrogen acts on the proximal promoter of the S6K1 gene in a mechanism involving the transcriptional factor GATA-3. Finally, we provide data that support the importance of estrogenic regulation of S6K1 expression in breast cancer cell proliferation. S6K1 directly phosphorylates and regulates ligand-independent activity of ERα, while ERα upregulates S6K1 expression. This S6K1–ERα relationship creates a positive feed-forward loop in control of breast cancer cell proliferation. Furthermore, the co-dependent association between S6K1 and ERα may be exploited in the development of targeted breast cancer therapies.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22286763</pmid><doi>10.1038/onc.2011.657</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/136/2091 631/67/1347 631/80/86 Animals Apoptosis Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer cells Cancer therapies Cell Biology Cell growth Cell Proliferation Cellular biology Data processing Development and progression Estradiol - pharmacology Estrogen Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Estrogen receptors Estrogens Feedback, Physiological Female GATA-3 protein GATA3 Transcription Factor - genetics GATA3 Transcription Factor - metabolism Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Genetic regulation Growth Health aspects Human Genetics Humans Internal Medicine Kinases Mammary Glands, Animal - drug effects Mammary Glands, Animal - metabolism MCF-7 Cells Medicine Medicine & Public Health Mice Mice, Inbred Strains Oncology original-article Phosphorylation Promoter Regions, Genetic Promoters Ribosomal protein S6 kinase Ribosomal Protein S6 Kinases, 70-kDa - genetics Ribosomal Protein S6 Kinases, 70-kDa - metabolism Tamoxifen - analogs & derivatives Tamoxifen - pharmacology Transcription Xenoestrogens |
| title | Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation |
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