ࡱ> 796q` RbjbjqPqP2&::    $0 l*H$ $ $ $ $ $ $ $h $ $   $ $ &    $ $      $ <   . <0l    ,$ Lp 6 , /$ $ $  $ $ $ l     Title:Induction of cell-cycle arrest by all-trans retinoic acid in mouse embryonic palatal mesenchymal (MEPM) cells Author(s): HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Yu+ZL&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Yu ZL,  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Lin+JX&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Lin JX,  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Xiao+Y&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Xiao Y,  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Han+J&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Han J,  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Zhang+XZ&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Zhang XZ,  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Jia+HC&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Jia HC,  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Tang+YN&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Tang YN,  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=OneClickSearch&field=AU&val=Li+Y&curr_doc=19/1&Form=FullRecordPage&doc=19/1" \o "one-click search" Li Y Source:TOXICOLOGICAL SCIENCES 83 (2): 349-354 FEB 2005 Document Type:Article Language:English  HYPERLINK "http://wos15.isiknowledge.com/CIW.cgi?SID=Z4on8i3kAbOj6mcc521&Func=PagedCitedRefList&UT=000226371400016&doc=19/1&rec_id=142625573" Cited References: 41 Times Cited: 0 HYPERLINK "Zengli%20Yu2005.pdf" \t "_blank" INCLUDEPICTURE "http://images.isiknowledge.com/WoK3/Images/Links/WOK3/Generic_Src.gif" \* MERGEFORMATINET  Abstract:all-trans retinoic acid (atRA), the oxidative metabolite of vitamin A, is essential for normal embryonic development. Also, high levels of atRA are teratogenic in many species and can effectively induce cleft palate in the mouse. Most cleft palate resulted from the failed fusion of secondary palate shelves, and maintenance of the normal cell proliferation is important in this process of shelf growth. To clarify the mechanism by which atRA causes cleft palate. we investigated the effect of atRA on proliferation activity and cell cycle distribution in mouse embryonic palatal mesenchymal (MEPM) cells. atRA inhibited the growth of MEPM cells by inducing apoptosis in a dose-dependent manner. atRA also caused a G1 block in the cell cycle with an increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S phase, as determined by flow cytometry. We next investigated the effects of atRA on molecules that regulate the G1 to S phase transition. These studies demonstrated that atRA inhibited expression of cyclins D and E at the protein level. Further-more, atRA treatment reduced phosphorylated Rb and decreased cdk2 and cdk4 kinase activity. These data suggest that atRA had antiproliferative activity by modulating GIN cell cycle regulators and by inhibition of Rb phosphorylation in MEPM cells, which might account for the pathogenesis of cleft palate induced by retinoic acid. Author Keywords:all-trans retinoic acid; mouse embryonic palatal mesenchymal cells; cell cycle; cyclins; retinoblastoma protein KeyWords Plus:RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; INDUCED APOPTOSIS; LEUKEMIA-CELLS; GROWTH; PHOSPHORYLATION; PROLIFERATION; PATHWAY; CARCINOMA; HEDGEHOG Addresses:Li Y (reprint author), Peking Univ, Sch Publ Hlth, Beijing, 100083 Peoples R China Peking Univ, Sch Publ Hlth, Beijing, 100083 Peoples R China Peking Univ, Sch Stomatol, Beijing, 100081 Peoples R China E-mail Addresses: HYPERLINK "mailto:liyong@bjmu.edu.cn" liyong@bjmu.edu.cn Publisher:OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND Subject Category:TOXICOLOGY IDS Number:888JY ISSN:1096-6080 tv5 6 ; < > ? p q v w y z 0 1 9 : < = жККККiККiККiККiККi,h.4h.4>*B*CJKHOJQJ^Jph2h.4h.45>*B*CJKHOJQJ\^Jph6jh.4h.4B*CJKHOJQJU^JaJph3h.4h.45B*CJKHOJQJ\^JaJph-h.4h.4B*CJKHOJQJ^JaJph/h.4h.45B*CJKHOJQJ\^Jph)vwMc,w $1$a$gd.4 $1$9Da$gd.4 optuw~kl}̵̵iS*hxB*CJKHOJQJ^JaJo(ph2h.4h.45>*B*CJKHOJQJ\^Jph3h.4h.45B*CJKHOJQJ\^JaJph/h.4h.45B*CJKHOJQJ\^Jph,h.4h.4>*B*CJKHOJQJ^Jph6jh.4h.4B*CJKHOJQJU^JaJph-h.4h.4B*CJKHOJQJ^JaJphGHIJKMVcq뫛lTlTlTlTlTl/h.4h.45B*CJKHOJQJ\^Jph-h.4h.4B*CJKHOJQJ^JaJph.jhrhxB*CJOJQJUaJphhxB*CJOJQJaJph(jhxB*CJOJQJUaJph4jhlhhlhB*CJOJQJUaJphhlhB*CJOJQJaJph(jhWB*CJOJQJUaJph)*,6w͙͞͞͞͞ ho(/h.4h.45B*CJKHOJQJ\^Jph,h.4h.4>*B*CJKHOJQJ^Jph-h.4h.4B*CJKHOJQJ^JaJph6jh.4h.4B*CJKHOJQJU^JaJph0182P. 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