|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2010-5-6
|
|
pubmed:abstractText |
The ErbB2 (Her2/neu epidermal growth receptor family) oncogene is overexpressed in 30% to 40% of human breast cancers. Cyclin D1 is the regulatory subunit of the holoenzyme that phosphorylates and inactivates the retinoblastoma (pRb) tumor suppressor and is an essential downstream target of ErbB2-induced tumor growth. Herein, we demonstrate that ErbB2 induces the activity of the Notch signaling pathway. ErbB2 induction of DNA synthesis, contact-independent growth, and mammosphere induction required Notch1. ErbB2-induced cyclin D1 and cyclin D1 expression was suficient to induce Notch1 activity, and conversely, genetic deletion of Notch1 in mammary epithelial cells using foxed Notch (Notch(fl/fl)) mice demonstrated that cyclin D1 is induced by Notch1. Genetic deletion of cyclin D1 or small interfering RNA (siRNA) to cyclin D1-reduced Notch1 activity and reintroduction of cyclin D1 into cyclin D1-deficient cells restored Notch1 activity through the inhibition of Numb, an endogenous inhibitor of Notch1 activity. Thus, cyclin D1 functions downstream as a genetic target of Notch1, amplifies Notch1 activity by repressing Numb, and identifies a novel pathway by which ErbB2 induces Notch1 activity via the induction of cyclin D1.
|
|
pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/N01CN43309,
http://linkedlifedata.com/resource/pubmed/grant/P30CA56036,
http://linkedlifedata.com/resource/pubmed/grant/R01-CA-098779,
http://linkedlifedata.com/resource/pubmed/grant/R01-CA-120876,
http://linkedlifedata.com/resource/pubmed/grant/R01-CA-80250,
http://linkedlifedata.com/resource/pubmed/grant/R01CA101841,
http://linkedlifedata.com/resource/pubmed/grant/R01CA111482,
http://linkedlifedata.com/resource/pubmed/grant/R01CA70896,
http://linkedlifedata.com/resource/pubmed/grant/R01CA75503,
http://linkedlifedata.com/resource/pubmed/grant/R01CA86071,
http://linkedlifedata.com/resource/pubmed/grant/R01CA86072
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/ERBB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neuregulin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
1752-8062
|
|
pubmed:author |
pubmed-author:AllenKathleen GKG,
pubmed-author:CasimiroMathew CMC,
pubmed-author:GeChanghuiC,
pubmed-author:GlazerRobert IRI,
pubmed-author:JiaoXuanmaoX,
pubmed-author:JuXiaomingX,
pubmed-author:KatiyarSanjayS,
pubmed-author:LiZhipingZ,
pubmed-author:LindsayJaimeJ,
pubmed-author:LisantiMichael PMP,
pubmed-author:LiuManranM,
pubmed-author:PestellRichard GRG,
pubmed-author:RaoMahadevM,
pubmed-author:RuiHallgeirH,
pubmed-author:SakamakiToshiyukiT,
pubmed-author:ShirleyLawrence ALA,
pubmed-author:StanleyPamelaP,
pubmed-author:TranThai HTH,
pubmed-author:WangChenguangC
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
1
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
107-15
|
|
pubmed:meshHeading |
pubmed-meshheading:20443831-Amyloid Precursor Protein Secretases,
pubmed-meshheading:20443831-Animals,
pubmed-meshheading:20443831-Breast Neoplasms,
pubmed-meshheading:20443831-Cell Line, Tumor,
pubmed-meshheading:20443831-Cyclin D1,
pubmed-meshheading:20443831-DNA, Neoplasm,
pubmed-meshheading:20443831-Female,
pubmed-meshheading:20443831-Humans,
pubmed-meshheading:20443831-Mice,
pubmed-meshheading:20443831-Neuregulin-1,
pubmed-meshheading:20443831-Receptor, Notch1,
pubmed-meshheading:20443831-Receptor, erbB-2,
pubmed-meshheading:20443831-Signal Transduction,
pubmed-meshheading:20443831-Tumor Stem Cell Assay
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
ErbB2 induces Notch1 activity and function in breast cancer cells.
|
|
pubmed:affiliation |
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
