Linked Life Data

12515730

Source:http://linkedlifedata.com/resource/pubmed/id/12515730

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-4-3
pubmed:abstractText
p27 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G(1)/S progression, and whose activity is, in part, regulated through interactions with D-type cyclins. Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation resulting in deregulated cyclin D1. We previously showed that p27 expression in MCL, as assessed by immunohistochemistry (IHC), does not show the usual inverse relationship to proliferate seen in most other lymphomas that do not overexpress cyclin D1. This suggested that the normal expression or control of p27 activity on cell growth might be altered through potential interactions with cyclin D1. Using Western blot and coimmunoprecipitation studies, we assessed the interrelationship between cyclin D1 and p27 in several cyclin D1(+) cell lines and primary MCL cases. Similar to our previous results by IHC, typical MCLs showed lower expression of p27 when compared to the more highly proliferative blastic cases or cell lines (mean arbitrary units: 58 versus 236 versus 120). Cyclin D1 was expressed at variable levels in both typical and blastic MCLs. p27 protein could be consistently coimmunoprecipitated with cyclin D1 from both cell lines and cases. Using techniques of exhaustive immunoprecipitation, we could demonstrate that most p27 protein was sequestered into complexes containing cyclin D1. We hypothesize that mantle cell lymphomagenesis results not only from direct consequences of inappropriate cyclin D1 expression, but also from the ability of overexpressed cyclin D1 to buffer physiologic changes in p27 levels, thereby rendering p27 ineffective as an inhibitor of cellular growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3181-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12515730-Antibodies, Monoclonal, pubmed-meshheading:12515730-Cell Cycle Proteins, pubmed-meshheading:12515730-Cell Division, pubmed-meshheading:12515730-Cell Transformation, Neoplastic, pubmed-meshheading:12515730-Chromosomes, Human, Pair 11, pubmed-meshheading:12515730-Chromosomes, Human, Pair 14, pubmed-meshheading:12515730-Cyclin D1, pubmed-meshheading:12515730-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:12515730-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12515730-Humans, pubmed-meshheading:12515730-Lymphoma, Mantle-Cell, pubmed-meshheading:12515730-Macromolecular Substances, pubmed-meshheading:12515730-Neoplasm Proteins, pubmed-meshheading:12515730-Neoplastic Stem Cells, pubmed-meshheading:12515730-Precipitin Tests, pubmed-meshheading:12515730-Protein Binding, pubmed-meshheading:12515730-Translocation, Genetic, pubmed-meshheading:12515730-Tumor Suppressor Proteins
pubmed:year
2003
pubmed:articleTitle
Sequestration of p27Kip1 protein by cyclin D1 in typical and blastic variants of mantle cell lymphoma (MCL): implications for pathogenesis.
pubmed:affiliation
Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't