Linked Life Data

10066798

Source:http://linkedlifedata.com/resource/pubmed/id/10066798

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-4-13
pubmed:abstractText
The cyclin D1 gene is overexpressed in breast tumors and encodes a regulatory subunit of cyclin-dependent kinases that phosphorylate the retinoblastoma protein. pp60(c-src) activity is frequently increased in breast tumors; however, the mechanisms governing pp60(c-src) regulation of the cell cycle in breast epithelium are poorly understood. In these studies, pp60(v-src) induced cyclin D1 protein levels and promoter activity (48-fold) in MCF7 cells. Cyclin D1-associated kinase activity and protein levels were increased in mammary tumors from murine mammary tumor virus-pp60(c-src527F) transgenic mice. Optimal induction of cyclin D1 by pp60(v-src) involved the extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase members of the mitogen-activated protein kinase family. Cyclin D1 promoter activation by pp60(v-src) involved a cAMP response element-binding protein (CREB)/activating transcription factor 2 (ATF-2) binding site. Dominant negative mutants of CREB and ATF-2 but not c-Jun inhibited pp60(v-src) induction of cyclin D1. pp60(v-src) induction of CREB was blocked by the p38 inhibitor SB203580 or by mutation of CREB at Ser133. pp60(v-src) induction of ATF-2 was abolished by the c-Jun N-terminal kinase inhibitor JNK-interacting protein-1 or by mutation of ATF-2 at Thr69 and Thr71. CREB and ATF-2, which bind to a common pp60(v-src) response element, are transcriptionally activated by distinct mitogen-activated protein kinases. Induction of cyclin D1 activity by pp60(v-src) may contribute to breast tumorigenesis through phosphorylation and inactivation of the retinoblastoma protein.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7341-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10066798-Activating Transcription Factor 2, pubmed-meshheading:10066798-Animals, pubmed-meshheading:10066798-Breast Neoplasms, pubmed-meshheading:10066798-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10066798-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:10066798-Cyclin D1, pubmed-meshheading:10066798-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10066798-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:10066798-Mice, pubmed-meshheading:10066798-Mice, Transgenic, pubmed-meshheading:10066798-Mitogen-Activated Protein Kinases, pubmed-meshheading:10066798-Oncogene Protein pp60(v-src), pubmed-meshheading:10066798-Plasmids, pubmed-meshheading:10066798-Promoter Regions, Genetic, pubmed-meshheading:10066798-Protein Binding, pubmed-meshheading:10066798-Signal Transduction, pubmed-meshheading:10066798-Transcription Factors, pubmed-meshheading:10066798-Tumor Cells, Cultured, pubmed-meshheading:10066798-p38 Mitogen-Activated Protein Kinases
pubmed:year
1999
pubmed:articleTitle
pp60(v-src) induction of cyclin D1 requires collaborative interactions between the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role for cAMP response element-binding protein and activating transcription factor-2 in pp60(v-src) signaling in breast cancer cells.
pubmed:affiliation
Departments of Developmental and Molecular Biology and Medicine, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't