Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis
THE D-type cyclins (Dl, D2 and D3) are critical governors of the cell-cycle clock apparatus during the Gl phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues 1,2 . To investigate why mammalian cells nee...
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| Veröffentlicht in: | Nature (London) 1996-12, Vol.384 (6608), p.470-474 |
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| creator | Sicinski, Piotr Donaher, Joana Liu Geng, Yan Parker, Susan B Gardner, Humphrey Park, Mary Y Robker, Rebecca L Richards, JoAnne S McGinnis, Lynda K Biggers, John D Eppig, John J Bronson, Roderick T Elledge, Stephen J Weinberg, Robert A |
| description | THE D-type cyclins (Dl, D2 and D3) are critical governors of the cell-cycle clock apparatus during the Gl phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues
1,2
. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2
−/−
ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA. |
| doi_str_mv | 10.1038/384470a0 |
| format | Article |
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1,2
. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2
−/−
ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/384470a0</identifier><identifier>PMID: 8945475</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biological and medical sciences ; Cell cycle, cell proliferation ; Cell Division - genetics ; Cell Division - physiology ; Cell physiology ; Cell Transformation, Neoplastic ; Cells, Cultured ; Colforsin - pharmacology ; Cyclic AMP - physiology ; Cyclin D2 ; Cyclins - genetics ; Cyclins - physiology ; Female ; Follicle Stimulating Hormone - physiology ; Fundamental and applied biological sciences. Psychology ; Gene Dosage ; Gene Expression Regulation ; Gene Targeting ; Granulosa Cells - cytology ; Humanities and Social Sciences ; Humans ; Infertility, Female - genetics ; letter ; Male ; Mammals ; Mice ; Molecular and cellular biology ; multidisciplinary ; Ovarian Neoplasms - metabolism ; Ovary - cytology ; Ovary - physiology ; RNA, Messenger - metabolism ; Science ; Science (multidisciplinary) ; Spermatogenesis - physiology ; Stem cells ; Testicular Neoplasms - metabolism ; Testis - cytology ; Testis - physiology ; Tumor Cells, Cultured</subject><ispartof>Nature (London), 1996-12, Vol.384 (6608), p.470-474</ispartof><rights>Springer Nature Limited 1996</rights><rights>1997 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 5, 1996</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4100-b1c01dab0e6b16490bf45032e6ce8062f981db75bf6bb0d57532f7d03cd03ecd3</citedby><cites>FETCH-LOGICAL-c4100-b1c01dab0e6b16490bf45032e6ce8062f981db75bf6bb0d57532f7d03cd03ecd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2495216$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8945475$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sicinski, Piotr</creatorcontrib><creatorcontrib>Donaher, Joana Liu</creatorcontrib><creatorcontrib>Geng, Yan</creatorcontrib><creatorcontrib>Parker, Susan B</creatorcontrib><creatorcontrib>Gardner, Humphrey</creatorcontrib><creatorcontrib>Park, Mary Y</creatorcontrib><creatorcontrib>Robker, Rebecca L</creatorcontrib><creatorcontrib>Richards, JoAnne S</creatorcontrib><creatorcontrib>McGinnis, Lynda K</creatorcontrib><creatorcontrib>Biggers, John D</creatorcontrib><creatorcontrib>Eppig, John J</creatorcontrib><creatorcontrib>Bronson, Roderick T</creatorcontrib><creatorcontrib>Elledge, Stephen J</creatorcontrib><creatorcontrib>Weinberg, Robert A</creatorcontrib><title>Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>THE D-type cyclins (Dl, D2 and D3) are critical governors of the cell-cycle clock apparatus during the Gl phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues
1,2
. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2
−/−
ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell cycle, cell proliferation</subject><subject>Cell Division - genetics</subject><subject>Cell Division - physiology</subject><subject>Cell physiology</subject><subject>Cell Transformation, Neoplastic</subject><subject>Cells, Cultured</subject><subject>Colforsin - pharmacology</subject><subject>Cyclic AMP - physiology</subject><subject>Cyclin D2</subject><subject>Cyclins - genetics</subject><subject>Cyclins - physiology</subject><subject>Female</subject><subject>Follicle Stimulating Hormone - physiology</subject><subject>Fundamental and applied biological sciences. 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Donaher, Joana Liu ; Geng, Yan ; Parker, Susan B ; Gardner, Humphrey ; Park, Mary Y ; Robker, Rebecca L ; Richards, JoAnne S ; McGinnis, Lynda K ; Biggers, John D ; Eppig, John J ; Bronson, Roderick T ; Elledge, Stephen J ; Weinberg, Robert A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4100-b1c01dab0e6b16490bf45032e6ce8062f981db75bf6bb0d57532f7d03cd03ecd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell cycle, cell proliferation</topic><topic>Cell Division - genetics</topic><topic>Cell Division - physiology</topic><topic>Cell physiology</topic><topic>Cell Transformation, Neoplastic</topic><topic>Cells, Cultured</topic><topic>Colforsin - pharmacology</topic><topic>Cyclic AMP - physiology</topic><topic>Cyclin D2</topic><topic>Cyclins - genetics</topic><topic>Cyclins - physiology</topic><topic>Female</topic><topic>Follicle Stimulating Hormone - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Dosage</topic><topic>Gene Expression Regulation</topic><topic>Gene Targeting</topic><topic>Granulosa Cells - cytology</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Infertility, Female - genetics</topic><topic>letter</topic><topic>Male</topic><topic>Mammals</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>multidisciplinary</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovary - cytology</topic><topic>Ovary - physiology</topic><topic>RNA, Messenger - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Spermatogenesis - physiology</topic><topic>Stem cells</topic><topic>Testicular Neoplasms - metabolism</topic><topic>Testis - cytology</topic><topic>Testis - physiology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sicinski, Piotr</creatorcontrib><creatorcontrib>Donaher, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sicinski, Piotr</au><au>Donaher, Joana Liu</au><au>Geng, Yan</au><au>Parker, Susan B</au><au>Gardner, Humphrey</au><au>Park, Mary Y</au><au>Robker, Rebecca L</au><au>Richards, JoAnne S</au><au>McGinnis, Lynda K</au><au>Biggers, John D</au><au>Eppig, John J</au><au>Bronson, Roderick T</au><au>Elledge, Stephen J</au><au>Weinberg, Robert A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>1996-12-05</date><risdate>1996</risdate><volume>384</volume><issue>6608</issue><spage>470</spage><epage>474</epage><pages>470-474</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>THE D-type cyclins (Dl, D2 and D3) are critical governors of the cell-cycle clock apparatus during the Gl phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues
1,2
. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2
−/−
ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>8945475</pmid><doi>10.1038/384470a0</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 1996-12, Vol.384 (6608), p.470-474 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_78579052 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Cell cycle, cell proliferation Cell Division - genetics Cell Division - physiology Cell physiology Cell Transformation, Neoplastic Cells, Cultured Colforsin - pharmacology Cyclic AMP - physiology Cyclin D2 Cyclins - genetics Cyclins - physiology Female Follicle Stimulating Hormone - physiology Fundamental and applied biological sciences. Psychology Gene Dosage Gene Expression Regulation Gene Targeting Granulosa Cells - cytology Humanities and Social Sciences Humans Infertility, Female - genetics letter Male Mammals Mice Molecular and cellular biology multidisciplinary Ovarian Neoplasms - metabolism Ovary - cytology Ovary - physiology RNA, Messenger - metabolism Science Science (multidisciplinary) Spermatogenesis - physiology Stem cells Testicular Neoplasms - metabolism Testis - cytology Testis - physiology Tumor Cells, Cultured |
| title | Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T23%3A30%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cyclin%20D2%20is%20an%20FSH-responsive%20gene%20involved%20in%20gonadal%20cell%20proliferation%20and%20oncogenesis&rft.jtitle=Nature%20(London)&rft.au=Sicinski,%20Piotr&rft.date=1996-12-05&rft.volume=384&rft.issue=6608&rft.spage=470&rft.epage=474&rft.pages=470-474&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/384470a0&rft_dat=%3Cproquest_cross%3E78579052%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=204455440&rft_id=info:pmid/8945475&rfr_iscdi=true |